Recent strategies on targeted delivery of thrombolytics

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英语作文-大数据分析助力医疗行业改革

英语作文-大数据分析助力医疗行业改革In recent years, the healthcare industry has undergone significant transformation, largely driven by advancements in big data analytics. This transformation is particularly evident in how big data is revolutionizing medical practices and contributing to reforms within the healthcare sector.Big data analytics involves the collection, processing, and analysis of vast amountsof data from various sources. In the context of healthcare, these sources can range from electronic health records (EHRs) and patient data to clinical trials and research studies. By harnessing the power of big data, healthcare providers and researchers can derive valuable insights that enhance patient care, improve operational efficiency, and drive evidence-based decision-making.One of the primary benefits of big data analytics in healthcare is its role in personalized medicine. Traditionally, medical treatments have been based on generalized guidelines that may not fully account for individual variations in genetics, lifestyle, and environmental factors. With big data analytics, healthcare professionals can analyze large datasets to identify patterns and trends specific to patient populations. This allows for the customization of treatment plans that are tailored to each patient's unique characteristics, thereby improving treatment outcomes and reducing the risk of adverse effects.Moreover, big data analytics enables predictive analytics in healthcare. By analyzing historical data and real-time information, predictive models can forecast potential health risks and outcomes for individual patients or larger populations. For example, predictive analytics can help identify patients at high risk of developing chronic conditions such as diabetes or cardiovascular disease. Early identification enables proactive interventions, such as lifestyle modifications or preemptive treatments, which can significantly reduce healthcare costs and improve patient outcomes.In addition to personalized medicine and predictive analytics, big data plays a crucial role in clinical decision support systems. These systems leverage data-driven insights to assist healthcare providers in making informed decisions at the point of care. For instance,diagnostic decision support systems can analyze symptoms, medical history, and diagnostic test results to generate differential diagnoses or recommend appropriate treatment protocols based on evidence-based guidelines and clinical best practices.Furthermore, big data analytics supports population health management initiatives. By aggregating and analyzing data from diverse sources, healthcare organizations can gain a comprehensive understanding of population health trends, disease prevalence, and healthcare utilization patterns within specific communities or regions. This holistic view enables targeted interventions, public health campaigns, and resource allocation strategies aimed at improving the overall health outcomes of populations.The integration of big data analytics with artificial intelligence (AI) and machine learning further enhances its capabilities in healthcare. AI-powered algorithms can continuously learn from new data inputs, refine predictive models, and identify complex patterns that may not be apparent through traditional statistical methods. This synergy enables healthcare providers to deliver more precise diagnoses, optimize treatment protocols, and streamline administrative processes, thereby fostering a more efficient and patient-centered healthcare delivery system.In conclusion, big data analytics represents a transformative force in the healthcare industry, driving reforms that prioritize personalized care, predictive insights, clinical decision support, and population health management. As technological advancements continue to evolve, the potential of big data to revolutionize medical practices and improve patient outcomes will only expand. Embracing and leveraging the power of big data analytics is essential for healthcare organizations seeking to thrive in an increasingly data-driven era of medicine.。

国际化策略英文

国际化策略英文Internationalization StrategyIntroductionIn today's globalized world, businesses are expanding their operations across borders to tap into new markets and gain a competitive advantage. This has led to an increased focus on internationalization strategies. An internationalization strategy refers to the plan and approach a company adopts to enter and operate in foreign markets successfully. In this essay, we will discuss the key components of a successful internationalization strategy and how these can be implemented.Market ResearchThe first step in developing an internationalization strategy is conducting thorough market research. This involves identifying potential markets and evaluating their attractiveness based on factors such as market size, growth potential, competition, and cultural fit. It is essential to understand the target market's demographics, consumer behavior, and preferences to adapt the company's products or services accordingly.Adaptation StrategyOnce the target markets have been identified, the next step is developing an adaptation strategy. This involves adapting the company's products or services to suit the unique needs and preferences of the target market. It may require making changes to the product design, packaging, pricing, or even the marketing message. For example, a food company expanding into a new country may need to modify its recipes to cater to local tastes andpreferences.Localization StrategyA crucial aspect of internationalization is the localization strategy. Localization refers to customizing the marketing message and communication to resonate with the target market. This includes translating marketing materials into the local language, using culturally appropriate imagery, and understanding the local nuances and customs. By effectively localizing their communication, companies can establish a strong connection with the target market, build brand loyalty, and gain a competitive edge. Distribution StrategyA robust distribution strategy is vital for successful internationalization. Companies need to identify and partner with suitable distribution channels in the target market. This could involve establishing partnerships with local distributors, wholesalers, or even setting up their own distribution networks. It is essential to understand the local distribution landscape, including customs, regulations, and logistics, to ensure efficient and timely delivery of products or services.Human ResourcesThe success of an internationalization strategy heavily relies on the capabilities and expertise of the human resources. Companies need to identify and recruit individuals who have knowledge of the target market, including its culture, language, and business practices. Additionally, training and development programs should be implemented to enhance cross-cultural understanding and help employees adapt to the new market. It may also be necessary tohire local talent to gain insights into the market and build strong relationships with local stakeholders.Risk ManagementInternational expansion comes with its share of risks and challenges. Therefore, a robust risk management strategy is essential. This involves identifying potential risks, such as economic volatility, political instability, legal and regulatory challenges, and developing contingency plans to mitigate these risks. It is important to constantly monitor and evaluate the market conditions and adjust the strategy accordingly.Case Study: NikeOne example of a company that has implemented a successful internationalization strategy is Nike. Nike is a global sports apparel and footwear company that has successfully entered and operated in multiple foreign markets. Nike's internationalization strategy focused on understanding local market trends, adapting its products, and leveraging local cultural insights in its marketing campaigns. Nike formed partnerships with local distributors and retailers and established a global supply chain network to ensure efficient delivery. The company also hired local talent to gain insights into the market and build strong relationships with local stakeholders. Through these strategies, Nike has been able to establish itself as a global leader in the sports apparel industry. ConclusionIn conclusion, developing a comprehensive internationalization strategy is crucial for businesses looking to expand into foreign markets. Market research, adaptation and localization strategies,distribution strategy, human resources, risk management, and understanding cultural nuances are all vital components of a successful internationalization plan. By implementing these strategies effectively, businesses can establish a strong presence, gain a competitive advantage, and achieve sustainable growth in new markets.Cooperation StrategyAnother important aspect of an internationalization strategy is the cooperation strategy. This involves identifying potential partners or collaborators in the target market that can provide valuable resources, expertise, and access to local networks. Collaboration with local partners can help businesses navigate the complexities of a new market, reduce risks, and accelerate their entry into the market.The choice of partners may vary depending on the nature of the business and the target market. It could include joint ventures with local companies, strategic alliances with industry players, or partnerships with distributors, suppliers, or retailers. The key is to find partners that have strong market knowledge and a good understanding of the local business environment.When forming partnerships, it is essential to establish clear objectives and roles for each party involved. This includes defining the scope of cooperation, resource-sharing, decision-making processes, and intellectual property rights. Open and transparent communication is crucial to ensure a successful collaboration. Cooperation strategies can also extend beyond just business partnerships. Engaging with local communities, industryassociations, and government agencies can provide valuable support and insights. These relationships can help businesses navigate regulatory frameworks, gain access to government incentives or grants, and build a positive reputation in the local market.Digital Expansion StrategyIn today's digital age, businesses cannot ignore the importance of a digital expansion strategy in their internationalization plans. The internet has significantly reduced barriers to entry into foreign markets, allowing businesses to reach global consumers with ease.A digital expansion strategy involves leveraging digital tools and platforms to market products or services, reach target customers, and facilitate transactions.A crucial aspect of a digital expansion strategy is the development of a localized online presence. This includes creating country-specific websites, mobile applications, and social media profiles that cater to the local market. Localization efforts should go beyond just translating content. It should consider cultural nuances, preferences, and online user behavior to create a seamless and personalized user experience.Digital marketing plays a vital role in a digital expansion strategy. Businesses should utilize various digital marketing channels such as search engine optimization (SEO), social media marketing, email marketing, and content marketing to reach and engage with their target audience. Targeted advertising campaigns can be developed to capture the attention of potential customers in thetarget market.E-commerce platforms are another essential component of a digital expansion strategy. Establishing partnerships with local e-commerce platforms or developing an in-house e-commerce platform can help businesses facilitate online transactions in the target market. E-commerce platforms should be optimized for local payment methods, languages, and delivery options to enhance the customer experience.Data analysis and insights should also be a priority when implementing a digital expansion strategy. By leveraging data analytics tools, businesses can gain valuable insights into customer behavior, preferences, and market trends. This data can guide business decisions and optimize marketing campaigns to maximize return on investment.Sustainability StrategyIn recent years, sustainability has become a critical consideration in business operations and strategies. Integrating sustainability into an internationalization strategy can provide businesses with a competitive advantage, enhance brand image, and meet the increasing consumer demand for environmentally and socially responsible products or services.A sustainability strategy in internationalization involves assessing and minimizing the environmental impact of business operations. This includes adopting sustainable manufacturing practices, reducing carbon emissions, optimizing energy usage, andimplementing waste management systems. Businesses should also consider sourcing sustainable materials and supporting suppliers that align with their sustainability values.In addition to environmental sustainability, social and ethical considerations should also be part of the strategy. Businesses should strive to create a positive impact on local communities, support fair trade practices, and ensure safe and fair working conditions for employees and suppliers. This can be achieved by establishing codes of conduct, conducting regular audits, and engaging in philanthropic initiatives.Transparent reporting and communication about sustainability practices are essential to build trust and credibility with consumers, stakeholders, and the local community. Businesses should regularly communicate their sustainability goals and progress through corporate social responsibility reports, annual sustainability audits, and public relations efforts. This transparency can help businesses differentiate themselves from competitors and attract conscious consumers.ConclusionAn internationalization strategy requires careful planning and execution to ensure successful entry into foreign markets. Market research, adaptation and localization strategies, distribution strategy, human resources, risk management, cooperation strategy, digital expansion strategy, and sustainability strategy are all critical components that businesses should consider. By implementing a comprehensive and well-thought-out internationalization strategy,businesses can overcome challenges, capture opportunities, and achieve sustained growth in global markets.。

(全面版)配送策略英文版

(全面版)配送策略英文版Comprehensive Delivery StrategyIn today's competitive market, having an effective delivery strategy is crucial for the success of any business. A well-thought-out delivery plan can help streamline operations, improve customer satisfaction, and ultimately increase profitability. In this document, we will explore a comprehensive delivery strategy that encompasses various aspects of the delivery process.1. Setting Clear ObjectivesThe first step in developing a successful delivery strategy is to define clear objectives. These objectives should align with the overall goals of the business and consider factors such as customer expectations, delivery timeframes, and budget constraints. By clearly outlining these objectives, businesses can better understand their delivery needs and tailor their strategies accordingly.2. Utilizing TechnologyTechnology plays a crucial role in modern delivery strategies. From route optimization software to real-time tracking systems, businesses can leverage technology to streamline their delivery operations, improve efficiency, and enhance the overall customer experience. By investing in the right technology solutions, businesses can stay ahead of the competition and meet the growing demands of today's consumers.3. Partnering with Reliable SuppliersPartnering with reliable suppliers is essential for ensuring a smooth and efficient delivery process. By working closely with suppliers who have a proven track record of timely deliveries and high-quality service, businesses can minimize delays, reduce costs, and maintain a high level of customer satisfaction. Building strong relationships with suppliers can also lead to long-term partnerships and mutual success.4. Implementing Sustainable PracticesIn today's environmentally conscious world, businesses are increasingly turning to sustainable delivery practices to reduce their carbon footprint and appeal to eco-conscious consumers. By implementing practices such as electric vehicles, reusable packaging, and carbon offset programs, businesses can demonstrate their commitment to sustainability while also reducing costs and improving their brand image.5. Monitoring and EvaluationContinuous monitoring and evaluation are key components of a successful delivery strategy. By tracking key performance indicators, analyzing delivery data, and seeking feedback from customers, businesses can identify areas for improvement, make necessary adjustments, and ensure that their delivery strategy remains effective and competitive. Regular reviews and audits can help businesses stay agile and responsive to changing market conditions.ConclusionA comprehensive delivery strategy is essential for the success of any business operating in today's fast-paced and competitive market. By setting clear objectives, leveraging technology, partnering with reliable suppliers, implementing sustainable practices, and monitoring performance, businesses can optimize their delivery operations, improve customer satisfaction, and achieve long-term success. By following the strategies outlined in this document, businesses can stay ahead of the competition and deliver exceptional service to their customers.。

chemical reviews模板

chemical reviews模板Chemical Reviews Template for "Advances in Drug Delivery Systems"Introduction:- The importance of drug delivery systems in ensuring the effective and targeted delivery of drugs- The need for advancements in drug delivery systems to improve therapy efficacy and reduce side effectsI. Overview of Drug Delivery SystemsA. Definition and purpose of drug delivery systemsB. Different types of drug delivery systems (e.g., nanoparticles, liposomes, hydrogels)C. Advantages and limitations of various drug delivery systemsII. Recent Advances in Drug Delivery SystemsA. Nanoparticles1. Importance of nanoparticles in drug delivery2. Types of nanoparticles used in drug delivery (e.g., polymeric nanoparticles, liposomes)3. Benefits of using nanoparticles for drug delivery (e.g.,enhanced drug stability, controlled release)4. Novel strategies for the preparation of nanoparticles (e.g., green synthesis, self-assembly techniques)5. Challenges and future prospects of nanoparticle-based drug delivery systemsB. Liposomes1. Introduction to liposomes as drug carriers2. Advantages of liposomes in drug delivery (e.g., biocompatibility, ability to encapsulate hydrophobic and hydrophilic drugs)3. Techniques for modifying the physicochemical properties of liposomes (e.g., surface functionalization, size control)4. Applications of liposomes in targeted drug delivery (e.g., tumor targeting, brain drug delivery)5. Current challenges and ongoing research in liposome-based drug deliveryC. Hydrogels1. Definition and characteristics of hydrogels2. Role of hydrogels in drug delivery (e.g., sustained release, protection of drugs)3. Types of hydrogels used in drug delivery (e.g., natural, synthetic)4. Approaches for controlling drug release from hydrogels (e.g., pH-responsive, temperature-responsive)5. Emerging trends and future prospects for hydrogel-based drug deliveryIII. Clinical Applications and OutcomesA. Successful examples of drug delivery systems in clinical practice1. Nanoformulations approved by regulatory authorities for drug delivery2. Liposomal drug delivery systems in use for specific disease treatments3. Hydrogel-based drug delivery systems in clinical trialsB. Improved therapy efficacy and patient outcomes1. Enhanced drug bioavailability and targeted delivery leading to improved therapy outcomes2. Reduction in side effects and toxicity through controlled release and protective drug delivery3. Case studies demonstrating improved patient adherence and treatment complianceIV. Challenges and Future DirectionsA. Current challenges in the development of drug delivery systems1. Regulatory hurdles and safety concerns2. Scalability and manufacturing challenges3. Cost-effectiveness and commercialization difficultiesB. Future directions and emerging trends in drug delivery systems1. Integration of nanotechnology with drug delivery systems2. Personalized drug delivery based on patient-specific factors3. Combination therapy using drug delivery systemsConclusion:- Recap of the importance of drug delivery systems for effective and targeted drug delivery- Summary of recent advances in nanoparticle, liposome, and hydrogel-based drug delivery systems- Discussion of clinical applications and outcomes, including improved therapy efficacy and patient outcomes- Highlighting the current challenges and future directions in the field of drug delivery systems。

TMG生产石墨烯

Triton Minerals LtdASX:ABN:Street address:Postal address:Tel:Fax:Email:**************************.au Web:.auProjects:Balama NorthAncuabeBalama SouthTMG PRODUCES GRAPHENEHIGHLIGHTS∙Trial production of Graphene Oxide completed∙Graphene Oxide readily produced from different graphite concentrate grades∙Commercial grade Graphene Oxide produced∙Graphene successfully produced∙TMG product range expandedTriton Minerals Limited(ASX: TON, Triton or Company) is pleased to announce the positive initial Graphene Oxide tests conducted on the TMG concentrates.Triton’s Managing Director & CEO Brad Boyle said: “The successful production of the Graphene Oxide and Graphene through standard industrial techniques, once again demonstrates the high quality and versatility of the TMG products.The remarkable properties of Graphene are well known and now that TMG has shown to be ideally suited to create the wonder material, this now creates further possibilities for Triton to expand their market presence and to explore an even broader client base and revenue streams.”GRAPHENE OXIDEIn tests conducted by a Government-sponsored laboratory in Singapore, Graphene Oxide has been successfully produced from various graphite concentrate grades of TMG product.Commercial-grade Graphene Oxide was readily produced from a broad range of TMG concentrates, using the standard extraction methods. These initial results are considered by Triton to be encouraging.In these industry-standard production runs only 1.5 grams of TMG concentrate was required to produce approximately 250ml of high concentration graphene oxide solution.Research has found that graphene oxide solution is sold commercially in a diluted form (concentration at 4mg/ml) and can sell for of up to $400 for 250ml. Triton considers that the economics of producing graphene oxideand subsequently graphene from TMG are very encouraging.The Company will continue to explore opportunities to refine the production of Graphene Oxide. As the predicted global demand for graphene oxide and graphene grows, Triton is well positioned to help meet that supply demand, with the ability to produce high purity and volume of graphite concentrate.Figure 1. Image of the Graphene Oxide solution (left) created from TMG concentrates. SEM Imaging of fine Graphene Oxide flakes (right) created from TMG concentrate. The size of the flakes ranged from approximately 100 nm to 3 μm.GRAPHENETriton confirms the same Singapore laboratory has also successfully created Graphene powder from the TMG products by simply reducing (drying) the TMG Graphene Oxide solution. Once the Graphene powder has been created it is actually insoluble in water.WHAT IS GRAPHENE OXIDEGraphene oxide (GO) is a unique material that can be viewed as a single monomolecular layer of graphite with various oxygen containing functionalities.Interest in GO has increased dramatically after graphene, a single layer of graphite, was first isolated and studied.Reduced GO can be made as a thin film from an aqueous dispersion of GO in water and has moderate conductivity, it is attractive for use in electronic devices. In addition to being components in electronic devices, GO and reduced GO have been used in nanocomposite materials, polymer composite materials, energy storage,biomedical applications, catalysis,and as a surfactant with some overlaps between these fields (Source: ).Figure 3. Graphene oxide (concentration level at 4 mg/mL, dispersion in H2O) PROPERTIES OF GRAPHENE OXIDEGraphene oxide is its easy dispersability in water and other organic solvents, as well as in different matrixes, due to the presence of the oxygen. The is a very important property when mixing the material with ceramic or polymer matrixes when trying to improve their electrical and mechanical properties. However, on the other hand, the electrical conductivity of GO is reduced and sometimes described as an electrical insulator, due to the bonding of the oxygen molecules (Source: ).There are many ways in which GO can be functionalized, depending on the desired application. For optoelectronics, biodevices or as a drug-delivery material, for example, it is possible to substitute amines for the organic covalent functionalization of graphene to increase the dispersability of chemically modified graphenes in organic solvents. It has also been proved that porphyrin-functionalized primary amines and fullerene-functionalized secondary amines could be attached to graphene oxide platelets, ultimately increasing nonlinear optical performance (Source: ).In order for GO to be usable as an intermediary in the creation of monolayer or few-layer graphene sheets, it is important to develop an oxidization and reduction process that is able to separate individual carbon layers and then isolate them without modifying their structure.GRAPHENE OXIDE APPLICATIONSThere are many applications which use GO and the list continues to grow. There are many obstacles needed to be overcome before GO can be used commercially in most areas but advancements are being made every day and some of the key areas of development for GO include bioengineering, composite materials, energy technology and nanotechnology.Energy StorageNanocomposites of reduced GO have been used for high capacity energy storage in lithium ion batteries. In these studies, electrically insulating metal oxide nanoparticles were adsorbed onto reduced GO to increase the performance of these materials in batteries. High surface area of reduced GO has been made using microwaves for exfoliation and reduction of GO. The high surface area reduced GO formed is useful as an energy storage material in super capacitors (Source: ).Graphene based micro-supercapacitors will likely be developed for use in low energy applications such as smart phones and portable computing devices. Graphene-enhanced lithium ion batteries could be used in much higher energy usage applications such as electrically powered vehicles, or they can be used as lithium ion batteries are now, in smartphones, laptops and tablet PCs but at significantly lower levels of size and weight (Source: ).Photovoltaic CellsOffering very low levels of light absorption (at around 2.7% of white light) whilst also offering high electron mobility means that graphene can be used as an alternative to silicon or ITO in the manufacture of photovoltaic cells. Silicon is currently widely used in the production of photovoltaic cells, but while silicon cells are very expensive to produce, graphene based cells are potentially much less so. When materials such as silicon turn light into electricity it produces a photon for every electron produced, meaning that a lot of potential energy is lost as heat. Recently published research has proved that when graphene absorbs a photon, it actually generates multiple electrons. Also, while silicon is able to generate electricity from certain wavelength bands of light, graphene is able to work on all wavelengths, meaning that graphene has the potential to be as efficient as, if not more efficient than silicon, ITO or (also widely used) gallium arsenide. Being flexible and thin means that graphene based photovoltaic cells could be used in clothing; to help recharge your mobile phone, or even used as retro-fitted photovoltaic window screens or curtains to help power your home (Source: ).ElectronicsIt is predicted that Optoelectronics; specifically touchscreens, liquid crystal displays (LCD) and organic light emitting diodes (OLEDs) will soon be using GO in a commercial volumes (Source: ). Other Electronic devices using GO as a starting material for at least one of the key components, including the field effect transistor (FET) that uses reduced GO as a chemical sensor and biosensor to detect hormonal catecholamine molecules, avidin and DNA. Whilst, another study had GO functionalised with glucose oxidase and deposited on an electrode was used as an electrochemical glucose sensor. (Source: ).UltrafiltrationAnother standout property of graphene is that while it allows water to pass through it, it is almost completely impervious to liquids and gases (even relatively small helium molecules). This means that graphene could be used as an ultrafiltration medium to act as a barrier between two substances. The benefit of using graphene is that it is only 1 single atom thick and can also be developed as a barrier that electronically measures strain and pressures between the 2 substances.This could mean that graphene is developed to be used in water filtration systems, desalination systems and efficient and economically more viable biofuel creation (Source: ).Composite MaterialsGraphene is strong, stiff and very light. Currently, aerospace engineers are incorporating carbon fibre into the production of aircraft as it is also very strong and light. However, graphene is much stronger whilst being also much lighter. Ultimately it is expected that graphene is utilized to create a material that can replace steel in the structure of aircraft, improving fuel efficiency, range and reducing weight. Due to its electrical conductivity, it could even be used to coat aircraft surface material to prevent electrical damage resulting from lightning strikes. In this example, the same graphene coating could also be used to measure strain rate, notifying the pilot of any changes in the stress levels that the aircraft wings are under. These characteristics can also help in the development of high strength requirement applications such as body armour for military personnel and vehicles (Source: ).Biomedical ApplicationsGO has been used as a component in drug delivery systems. Functionalized nanographene oxide has been used in several studies on targeted delivery of anti-cancer drugs (Source: ).BiosensorsGO and reduced GO have been used as components in several systems designed to detect biologically relevant molecules. Folic acid functionalized GO was used as a component in a system used to detect human cervical cancer and human breast cancer cells (Source: ).CONVERTING GRAPHITE TO GRAPHENE OXIDETriton confirms that there are many ways being developed by companies around the world to produce commercial volumes of GO and graphene, however, at the moment the most popular method to produce graphene is by using mechanical or thermal exfoliation, chemical vapour deposition (CVD), and epitaxial growth.Many modern procedures for the synthesis of GO are based on the method first reported by Hummers in which graphite is oxidized by a solution of potassium permanganate in sulphuric acid. Reduction of GO has been reported using hydrazine, NaBH4, ascorbic acid, and HI. GO can be reduced as a thin film or in an aqueous solution (Source: ).It appears the most effective way of synthesised graphene on a large scale is through chemical reduction of graphene oxide. However, it has been difficult for scientists to complete the task of producing graphene sheets of the same quality as mechanical exfoliation (Source: ). Interest in GO continues to grow as people search for a cheaper, simpler, more efficient and better yielding method of producing graphene, that can be scaled up massively compared to current methods, and be financially suitable for industrial or commercial applications. Once this issue is overcome, we can expect to see graphene become much more widely used in commercial and industrial applications (Source: ).CONCLUSIONS – What does this mean for Triton?The demand and use of Graphene Oxide and Graphene continues to grow rapidly around the world in areas of bioengineering, composite materials, energy technology and nanotechnology. Triton has successfully produced Graphene Oxide and Graphene, using industry-standard methods, from the TMG concentrate.This further demonstrates the high quality and versatility of the TMG concentrate products and creates further possibilities for Triton to expand their market presence and to explore a broader customer and application base and revenue stream.Triton is rapidly working towards establishing TMG as a new global graphite-industry benchmark, by aiming to offer the world's lowest cost and most diversified graphite product range together with the longevity of a reliable supply of high quality flake graphite.RegardsBrad BoyleCEO & Managing DirectorTriton Minerals LtdHolder of the world’s largest known combined graphite-vanadium resourceVisionLed by a highly experienced Board and Management team, Triton’s primary vision is to grow shareholders value through discovery and development of graphite, gold and other precious, base and industrial minerals deposits. Further, Triton will explore vertical integration opportunities to supplement its core business and to create valued revenue streams to ultimately benefit Triton’s shareholders.TMG and beyondTriton hopes to establish Triton Mozambique graphite, produced from its Mozambique graphite projects (TMG) as the global graphite-industry benchmark by aiming to offer the world’s lowest cost and most diversified graphite product range, together with the longevity of a reliable supply of high quality flake graphite.Triton hopes to establish Triton Mozambique graphite, produced from its Mozambique graphite projects (TMG) as the global graphite-industry benchmark.Triton is also actively pursuing vertical integration opportunities to be involved in all aspects of the graphite supply chain, which Triton believes will add significant value to the Company and its shareholders in the long term.For further information, please contact:Brad BoyleCEO & Managing DirectorTel: + 61 8 6489 2555Email: ****************************.auForward-Looking StatementsThis document may include forward-looking statements. Forward-looking statements include, but are not necessarily limited to, statements concerning Triton Minerals Limited’s planned exploration program and other statements that are not historic facts. When used in this document, th e words such as “could”, “plan”, “estimate” “expect”, “intend”, “may”, “potential”, “should” and similar expressions are forward-looking statements. Although Triton Minerals Limited believes that its expectations reflected in these are reasonable, such statements involve risks and uncertainties, and no assurance can be given that actual results will be consistent with these forward-looking statements.。

配送计划的英语

配送计划的英语Delivery plans play a crucial role in the success of any business that relies on the timely and efficient distribution of goods or services. In today's fast-paced and highly competitive market, a well-crafted delivery plan can be the difference between a thriving enterprise and one that struggles to keep up with the demands of its customers. This essay will delve into the key components of an effective delivery plan and explore the strategies and considerations that businesses must take into account to ensure the smooth and reliable transportation of their products.At the heart of any successful delivery plan is a deep understanding of the company's target market and the unique needs and expectations of its customers. Businesses must carefully analyze factors such as geographic location, delivery time requirements, and preferred shipping methods to develop a plan that caters to the specific needs of their clientele. This may involve the establishment of strategic partnerships with logistics providers, the implementation of advanced tracking and monitoring systems, or the optimization of delivery routes to minimize travel time and fuel consumption.One of the primary considerations in a delivery plan is the selection of the appropriate transportation mode. Depending on the nature of the products being delivered, the distance to be covered, and the urgency of the shipment, businesses may choose from a variety of options, including ground transportation, air freight, or a combination of both. Ground transportation, such as trucks or vans, is often the most cost-effective option for local or regional deliveries, while air freight may be necessary for time-sensitive or long-distance shipments. The decision-making process must take into account not only the cost but also the reliability, speed, and environmental impact of each transportation mode.In addition to the selection of the appropriate transportation method, a comprehensive delivery plan must also address the issue of inventory management. Businesses must carefully balance the need to maintain adequate stock levels to meet customer demand with the costs associated with storing and managing that inventory. This may involve the implementation of just-in-time (JIT) inventory systems, which aim to minimize the amount of inventory on hand by coordinating the delivery of goods with the actual demand for those products. Effective inventory management can help to reduce storage costs, minimize the risk of spoilage or obsolescence, and ensure that customers receive their orders in a timely manner.Another crucial aspect of a delivery plan is the optimization of the logistics and distribution network. This may involve the strategic placement of warehouses or distribution centers, the establishment of efficient delivery routes, and the utilization of advanced tracking and monitoring technologies. By streamlining the logistics of their delivery operations, businesses can reduce the time and resources required to transport goods, ultimately leading to faster delivery times and lower operational costs.In today's increasingly global and interconnected marketplace, businesses must also consider the challenges and complexities associated with international deliveries. This may involve navigating customs regulations, managing currency exchange rates, and ensuring compliance with local laws and regulations. Effective communication with overseas partners and customers, as well as the implementation of robust risk management strategies, are essential for the successful execution of international delivery plans.Finally, the success of a delivery plan is heavily dependent on the quality of customer service and the ability of the business to respond to the changing needs and expectations of its clientele. This may involve the provision of real-time tracking information, the establishment of clear and transparent communication channels, and the implementation of flexible delivery options to accommodate the diverse needs of customers. By prioritizing customer satisfaction andcontinuously seeking feedback, businesses can refine and improve their delivery plans to better meet the evolving demands of the market.In conclusion, the development and implementation of an effective delivery plan is a critical component of any successful business strategy. By considering the unique needs and expectations of their customers, optimizing their logistics and distribution networks, and adapting to the ever-changing landscape of the global marketplace, businesses can ensure the timely and reliable delivery of their products, ultimately driving customer loyalty and enhancing their competitive edge. As the world becomes increasingly interconnected and the demands of consumers continue to evolve, the importance of a well-crafted delivery plan will only continue to grow, making it a vital area of focus for businesses of all sizes and industries.。

英语作文-国内外电信行业企业创新能力研究与对策分析

英语作文-国内外电信行业企业创新能力研究与对策分析In recent years, the telecommunications industry, both domestically and internationally, has undergone significant transformations driven by innovation capabilities within companies. This transformation has been crucial as it has not only enhanced operational efficiency but also revolutionized service delivery and customer experience across the globe.Telecommunications firms are increasingly focusing on enhancing their innovation capabilities to stay competitive in a rapidly evolving market landscape. Innovation in this sector encompasses technological advancements, strategic partnerships, and novel service offerings that cater to the growing demands of consumers and businesses alike.At the forefront of innovation are advancements in telecommunications infrastructure. Companies are investing heavily in next-generation networks such as 5G, which promise higher speeds, lower latency, and greater connectivity. These technological advancements not only improve consumer experience but also enable new applications in sectors ranging from healthcare to manufacturing.Moreover, innovation within telecommunications extends beyond infrastructure. Companies are leveraging big data analytics to gain insights into consumer behavior and preferences, allowing for personalized services and targeted marketing strategies. Artificial intelligence (AI) plays a pivotal role in optimizing network management and predicting maintenance needs, thereby enhancing operational efficiency and reducing costs.On a global scale, telecommunications firms are also exploring collaborative innovation strategies. Strategic alliances and partnerships with technology providers, startups, and research institutions facilitate the exchange of knowledge and resources, accelerating the pace of innovation. These collaborations often result in breakthrough technologies and solutions that address complex industry challenges.Furthermore, regulatory frameworks play a crucial role in shaping innovation within the telecommunications sector. Governments and regulatory bodies are increasingly adopting policies that foster competition while ensuring consumer protection and data privacy. Clear and consistent regulatory environments provide companies with the certainty needed to invest in long-term innovation initiatives.In response to these dynamics, telecommunications companies are adopting proactive approaches to enhance their innovation capabilities. Continuous investment in research and development (R&D) enables firms to pioneer new technologies and solutions ahead of competitors. Cross-functional teams comprising engineers, data scientists, and business strategists collaborate closely to ideate, prototype, and commercialize innovative products and services.Additionally, fostering a culture of innovation within organizations is essential for sustained growth and competitiveness. Companies encourage employees at all levels to contribute ideas and suggestions, creating a fertile ground for innovation. Employee training programs and incentives further reinforce this culture, ensuring that innovation remains a core organizational value.Looking ahead, the telecommunications industry is poised for further transformation driven by emerging technologies such as Internet of Things (IoT), blockchain, and edge computing. These technologies have the potential to unlock new revenue streams and redefine business models, further underscoring the importance of continuous innovation.In conclusion, the ability of telecommunications firms to innovate effectively will determine their success in an increasingly digital and interconnected world. By investing in advanced technologies, forging strategic partnerships, navigating regulatory landscapes, and nurturing a culture of innovation, companies can position themselves as leaders in the global marketplace. Embracing innovation not only drives growth and profitability but also enables companies to meet the evolving needs of customers and society at large, thereby ensuring long-term sustainability and competitiveness.。

英语作文-如何提高快递服务的效率和质量

英语作文-如何提高快递服务的效率和质量Improving Efficiency and Quality in Courier Services。

Efficient and high-quality courier services are crucial in today's fast-paced world where speed and reliability are paramount. Whether delivering documents, packages, or goods, optimizing delivery processes can significantly enhance customer satisfaction and operational efficiency. This article explores various strategies to achieve these goals.Firstly, investing in advanced tracking and logistics technologies is indispensable. Real-time tracking systems enable both the courier company and customers to monitor the shipment's progress accurately. This transparency not only builds trust but also allows proactive management of potential delays or issues. Integrating GPS technology with delivery vehicles ensures optimal route planning, minimizing travel time and fuel consumption.Secondly, streamlining operational workflows is essential. From sorting packages to dispatching delivery personnel, every step should be optimized for efficiency. Implementing barcode scanning and automated sorting systems can expedite package handling and reduce human errors. Moreover, adopting a centralized warehouse management system facilitates inventory control and quicker retrieval of items, ensuring timely dispatch.Ensuring a well-trained and motivated workforce is equally critical. Couriers should undergo comprehensive training in customer service, efficient driving techniques, and using technology effectively. Motivating employees through recognition programs and performance incentives fosters a culture of excellence and dedication to service quality. Additionally, cultivating a responsive customer support team capable of promptly addressing inquiries or issues contributes significantly to overall service satisfaction.Furthermore, leveraging data analytics provides invaluable insights for continuous improvement. Analyzing delivery performance metrics such as delivery times, successful deliveries versus returns, and customer feedback helps identify areas needingenhancement. For instance, identifying frequently occurring delivery challenges allows for targeted solutions and process adjustments to prevent recurrence.Collaboration with partners and stakeholders in the supply chain enhances operational synergy. Establishing strong partnerships with suppliers, local authorities, and other stakeholders ensures smooth logistics operations. Coordination with local governments for optimized traffic management during peak hours or adverse weather conditions can mitigate delays and improve service reliability.To enhance service quality, implementing stringent quality control measures is imperative. Regular audits of delivery processes, vehicle maintenance checks, and adherence to safety protocols are essential. Maintaining high standards ensures that deliveries are not only efficient but also safe and secure, thereby building customer confidence.Lastly, embracing innovation and adapting to evolving customer expectations are key to staying competitive. Introducing flexible delivery options such as same-day or time-slot deliveries caters to diverse customer needs. Embracing sustainable practices, such as eco-friendly packaging and electric delivery vehicles, not only reduces environmental impact but also appeals to environmentally conscious consumers.In conclusion, enhancing efficiency and quality in courier services requires a multifaceted approach encompassing technology integration, streamlined operations, workforce empowerment, data-driven insights, collaboration, quality control, and innovation. By continually refining processes and embracing advancements, courier companies can achieve higher customer satisfaction, operational efficiency, and sustainable growth in the competitive logistics industry.。

2024年亚洲心肺复苏研究进展英文版

2024年亚洲心肺复苏研究进展英文版Research Progress on Cardiopulmonary Resuscitation in Asia in 2024In 2024, the field of cardiopulmonary resuscitation (CPR) in Asia has seen significant advancements. Various studies have focused on improving survival rates and outcomes for individuals experiencing cardiac arrest. Research has emphasized the importance of early recognition of cardiac arrest, prompt initiation of CPR, and effective post-resuscitation care.One key area of progress is the integration of technology into CPR training and delivery. Virtual reality simulations and mobile applications have been developed to enhance CPR education and provide real-time guidance during resuscitation efforts. These technological advancements aim to improve the quality of CPR performed by both healthcare professionals and laypersons.Additionally, research has highlighted the importance of bystander CPR in improving survival rates. Community-based CPR training programs have been implemented to empower individuals to respond effectively in emergency situations. These programs have been successful in increasing bystander CPR rates and ultimately saving more lives.Furthermore, studies have explored the use of novel CPR techniques and devices to improve outcomes. From mechanical CPR devices to targeted temperature management strategies, researchers have been investigating innovative approaches to enhance resuscitation efforts and optimize patient outcomes.Overall, the research progress on cardiopulmonary resuscitation in Asia in 2024 reflects a commitment to improving the quality of care for individuals experiencing cardiac arrest. By leveraging technology, promoting bystander CPR, and exploring novel techniques, researchers are working towards enhancing survival rates and outcomes in the region.。

优化医疗服务模式的措施

优化医疗服务模式的措施英文回答：Measures to Optimize Healthcare Delivery Models.Optimizing healthcare delivery models is crucial for improving patient outcomes, enhancing accessibility, and reducing healthcare costs. By implementing effective measures, healthcare providers can create a more efficient and equitable healthcare system. Here are key measures to optimize healthcare delivery models:Value-Based Care: Shifting from fee-for-service models to value-based care models rewards providers based on patient outcomes and quality of care, rather than the quantity of services provided. This encourages providers to focus on preventive care, chronic disease management, and overall patient well-being.Telehealth: Leveraging technology to provide remotehealthcare services, telehealth expands access to care, particularly for patients in rural or underserved areas. It allows patients to connect with providers virtually, reducing travel time and costs, and improving convenience.Home-Based Care: Providing healthcare services in the comfort of patients' homes can enhance patient satisfaction, reduce hospital readmissions, and lower costs. Home-based care models utilize technology to monitor patients remotely, provide medication management, and offer a range of other services.Care Coordination: Implementing care coordination programs helps streamline communication and collaboration among healthcare providers, patients, and caregivers. Care coordinators ensure that patients receive appropriate care, avoid unnecessary duplications, and have a seamlesstransition between different healthcare settings.Personalized Medicine: Utilizing genetic information and other data to tailor healthcare interventions to individual patients' needs, personalized medicine offersmore precise diagnoses and targeted treatments. This approach can improve outcomes and reduce the risk ofadverse reactions.Data Analytics: Harnessing data analytics to analyze patient information, identify trends, and predict health risks enables healthcare providers to make informed decisions, improve care management, and allocate resources more efficiently.Patient Engagement: Empowering patients to actively participate in their healthcare decision-making enhances their engagement and adherence to treatment plans. Patient portals, shared decision-making models, and health literacy initiatives foster patient involvement and improve outcomes.Interdisciplinary Collaboration: Breaking down silos and fostering collaboration among different healthcare professionals, including physicians, nurses, pharmacists, and social workers, leads to a more comprehensive and coordinated approach to patient care.Community-Based Care: Establishing partnerships with community organizations and resources can provide patients with access to social support, mental health services, affordable housing, and other essential services that contribute to overall health and well-being.Health Equity: Addressing health disparities and promoting equitable access to healthcare for all populations, regardless of race, ethnicity, income, or geographic location, is essential for optimizing healthcare delivery models. Interventions include targeted outreach programs, culturally sensitive care, and reducing financial barriers.By implementing these measures, healthcare providers can optimize healthcare delivery models to enhance patient care, reduce costs, and create a more equitable andefficient healthcare system.中文回答：优化医疗服务模式的措施。

生产交付能力提升流程制度

生产交付能力提升流程制度Improving production and delivery capabilities is crucial for any business looking to stay competitive in today's fast-paced market. 提升生产交付能力对于任何企业来说都至关重要，这是在当今快节奏市场中保持竞争力的必要条件。

By streamlining processes and implementing effective systems, companies can ensure that they are able to meet customer demands in a timely manner. 通过简化流程和实施有效的系统，企业可以确保他们能够及时满足客户的需求。

This involves a combination of optimizing production workflows, improving supply chain management, and fostering a culture of continuous improvement. 这涉及优化生产工作流程，改善供应链管理，并培养持续改进的文化。

By focusing on these areas, businesses can increase their efficiency, reduce lead times, and ultimately enhance their overall competitiveness. 通过专注于这些领域，企业可以提高效率，缩短交货周期，并最终增强其整体竞争力。

One key aspect of improving production and delivery capabilities is the need to invest in technology and automation. 提升生产交付能力的一个关键方面是需要投资于技术和自动化。

大容量注射剂装量标准

大容量注射剂装量标准English Answer:Definition of a Large Volume Parenteral (LVP)。

A large volume parenteral (LVP) is a sterile, injectable solution or suspension that is administered in volumes greater than 100 mL and must be diluted prior to administration. LVPs are typically used to provide fluid and electrolyte replacement, nutrition, or medication delivery.Standard Fill Volumes for LVPs.The standard fill volumes for LVPs vary depending on the type of solution or suspension and the intended use. Common fill volumes include:50 mL.100 mL.250 mL.500 mL.1000 mL.Factors Influencing Fill Volume.Several factors can influence the fill volume of an LVP, including:Type of solution or suspension: Different solutionsand suspensions have different viscosities and densities, which affect the volume required to provide the desired dose.Intended use: The intended use of the LVP, such asfluid replacement, nutrition, or medication delivery, determines the volume required to achieve the desired therapeutic effect.Patient size: The size and weight of the patient can influence the volume of LVP required to meet their fluidand nutritional needs.Frequency of administration: The frequency of LVP administration, such as daily or weekly, affects the total volume required over a given period.Regulatory Considerations.The fill volume of LVPs is regulated by various regulatory agencies worldwide, such as the United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA). These agencies establish standardsto ensure the safety, efficacy, and quality of LVP products.Challenges in Fill Volume Determination.Determining the optimal fill volume for an LVP can be challenging, as it requires careful consideration ofmultiple factors. To ensure the appropriate fill volume,manufacturers conduct extensive testing and clinical trials to evaluate the safety, efficacy, and stability of their products.Recent Advancements.Recent advancements in technology have led to the development of new LVP formulations and delivery systems that allow for more targeted and individualized therapy. These advancements include:Concentrated solutions: Concentrated solutions require a smaller fill volume to provide the same dose, reducing the risk of fluid overload.Multi-chamber bags: Multi-chamber bags allow for the simultaneous administration of multiple solutions or medications, reducing the number of infusions needed.Smart infusion systems: Smart infusion systems monitor and adjust the flow rate of LVPs based on patient parameters, ensuring optimal fluid delivery.Conclusion.The fill volume of large volume parenterals (LVPs) is a critical aspect of safe and effective therapy. Standardfill volumes are established based on various factors, including the type of solution or suspension, intended use, patient size, frequency of administration, and regulatory considerations. Ongoing advancements in technology are enabling the development of more targeted andindividualized LVP therapies.Chinese Answer:大容量注射剂装量标准。

药学类作文模板英语翻译

药学类作文模板英语翻译Title: Pharmaceutical Essay Template。

Introduction。

In recent years, the field of pharmaceuticals has become increasingly important in the healthcare industry. The development of new drugs and the improvement of existing medications have a direct impact on the well-being of individuals around the world. In this essay, we will explore the key components of pharmaceutical research and development, as well as the ethical considerations that come into play.The Drug Development Process。

The process of developing a new drug is a complex and time-consuming endeavor that involves multiple stages. It typically begins with the discovery of a potential new compound, either through laboratory research or through the screening of natural substances. Once a promising compound has been identified, it undergoes preclinical testing to assess its safety and efficacy. This stage involves extensive animal testing to determine the compound's effects on living organisms.If the results of the preclinical testing are favorable, the compound then moves into clinical trials, which are conducted in human subjects. These trials are designed to evaluate the safety and effectiveness of the drug, as well as to determine the appropriate dosage and administration methods. Clinical trials are typically conducted in three phases, each involving a larger number of participants than the previous phase. If the drug is found to be safe and effective in these trials, it may then receive approval from regulatory agencies such as the Food and Drug Administration (FDA) in the United States.Ethical Considerations。

长链酰基辅酶a脱氢酶的乙酰化___概述说明

长链酰基辅酶a脱氢酶的乙酰化概述说明1. 引言1.1 概述长链酰基辅酶A脱氢酶（long-chain acyl-CoA dehydrogenase, LCAD）是一种重要的酶类，参与人体脂肪酸代谢过程中的乙酰化反应。

乙酰化作为脂肪酸代谢过程中的关键步骤，对于维持机体正常能量代谢和生理功能发挥着重要作用。

LCAD作为乙酰化的关键调节因子，在细胞内参与长链脂肪酸的氧化解聚反应，并在线粒体内催化乙酰辛二烯CoA转变成顺丁烯二烯CoA。

本文将详细探讨LCAD在乙酰化反应中的功能和生理意义，以及目前对其乙酰化机制进行的研究进展。

1.2 文章结构本文主要分为五个部分：引言、长链酰基辅酶A脱氢酶的乙酰化、实验方法和技术应用、讨论与总结以及结论。

引言部分将介绍本文的概述、文章结构和目的；长链酰基辅酶A脱氢酶的乙酰化部分将详细探讨LCAD的功能和生理意义，以及乙酰化机制的研究进展；实验方法和技术应用部分将介绍相关的实验方法和技术应用前景；讨论与总结部分将对结果进行解读并进行讨论，同时指出研究的局限性与不足之处；最后，通过结论对整篇文章进行总结。

1.3 目的本文的目的在于系统地概述长链酰基辅酶A脱氢酶的乙酰化过程，并对其功能、生理意义以及研究进展进行深入探讨。

通过对LCAD乙酰化机制和调控方式的研究，我们可以更好地了解脂肪酸代谢过程中关键步骤的调节和影响因素，并为深入揭示相关代谢疾病发生机制提供理论依据。

此外，还可以为开发新型药物或治疗策略提供重要参考依据，从而促进健康领域的发展。

2. 长链酰基辅酶A脱氢酶的乙酰化2.1 长链酰基辅酶A脱氢酶的功能和作用长链酰基辅酶A脱氢酶（long-chain acyl-CoA dehydrogenase，LCAD）是一种重要的线粒体内脂肪代谢相关的肽链。

它在β-氧化过程中发挥着关键作用。

其主要功能是促使长链脂肪酸与辅酶A结合形成合成物，并催化这个复合物在细胞线粒体内进行氧化反应。

大客户销售决策谋略(英文版)

大客户销售决策谋略(英文版)In today's highly competitive business environment, selling to big clients is crucial for the success and growth of any organization. However, securing sales with major clients requires careful planning and strategic decision-making. Here are some strategies that can help sales teams effectively sell to big customers:1. Research and Identify Potential Big Clients:Before approaching big clients, conducting thorough market research is essential. This research should focus on identifying major companies in the target industry that have a need for the products or services offered by the selling organization. Identifying the right big clients is crucial to determine the potential return on investment and maximize the chances of success.2. Understand the Client's Needs and Pain Points:To sell effectively to big clients, it is important to understand their specific needs and pain points. Conducting in-depth conversations and consultations with key decision-makers at the client's organization will help uncover their unique challenges and requirements. This knowledge will enable sales teams to tailor their approach and solution to provide maximum value to the client.3. Build Strong Relationships:Building strong relationships with big clients is vital for long-term success. Sales teams should invest time and effort in developing meaningful connections with key stakeholders within the client's organization. This involves regular communication, networking, personalized engagement, and providing exceptional customer service. These efforts will help create trust, loyalty, and a strongreferral base.4. Demonstrate Value and Differentiation:To win over big clients, sales teams must clearly communicate the value proposition and unique selling points of their products or services. It is essential to demonstrate how the offering can solve the client's challenges and improve their business performance. Sales teams should focus on highlighting the competitive advantages, such as cost savings, efficiency improvements, increased revenue, or customer satisfaction, that the client can expect to gain by choosing their organization.5. Provide Superior Post-Sale Support:Big clients expect a high level of service and support post-sale. Sales teams should ensure a smooth onboarding process and provide ongoing assistance and guidance to the client. Timely response to inquiries, accurate order fulfillment, and proactive troubleshooting are key aspects of superior post-sale support. This will not only help build long-term relationships but also lead to potential upselling or repeat business from satisfied clients.6. Adapt and Customize the Offering:Big clients often have unique requirements that differ from smaller customers. Sales teams must be willing to adapt and customize their product or service to meet these specific needs. This may involve modifications to the product, contract terms, pricing, or other aspects of the offering. Flexibility and willingness to accommodate the client's demands will significantly increase the chances of securing the sale.In conclusion, successfully selling to big clients requires a strategic approach that focuses on thorough research, understanding client needs, building relationships, demonstrating value, providing excellent post-sale support, and adapting to the client's requirements. By implementing these strategies, sales teams can enhance their chances of closing deals with big clients and driving business growth.Selling to big clients is not an easy task. It requires a dedicated effort and a strategic approach. Here are some additional strategies to consider when selling to big clients:7. Develop a Strong Value Proposition:To stand out from the competition, it is important to develop a compelling value proposition that clearly articulates why the client should choose your organization over others. The value proposition should highlight the unique benefits and advantages of your product or service and demonstrate how it can solve the client's pain points or challenges. It should be tailored to the specific needs and goals of the client, and should be communicated effectively during sales presentations and discussions.8. Create a Customized Sales Approach:Every big client is unique, and a one-size-fits-all sales approach is unlikely to be effective. Tailor your sales approach to each individual client by understanding their business objectives, industry trends, and competitive landscape. This customized approach should address the client's specific pain points and demonstrate how your offering can help them achieve their goals. This will show the client that you have taken the time to understand their needs and are invested in their success.9. Leverage Testimonials and Case Studies:Big clients often want to see evidence of your organization's track record and success. Leverage testimonials and case studies from previous clients to demonstrate your capabilities and effectiveness. Highlight successful implementations, positive results, and satisfied clients. This social proof can help build confidence and trust with potential big clients and showcase your ability to deliver on promises.10. Highlight Industry Expertise and Thought Leadership: Showcasing your organization's industry expertise and thought leadership can be a powerful tool when selling to big clients. Share relevant industry insights, trends, and best practices with the client to position yourself as an authority and trusted advisor. Share whitepapers, articles, and educational materials that showcase your knowledge and expertise. This will not only build credibility but also establish your organization as a valuable resource for the client.11. Leverage Networking and Referral Opportunities:Big clients often have a wide network of connections in the industry. Engage in networking activities and attend industry events to meet potential big clients and build relationships. Additionally, encourage satisfied clients to provide referrals or testimonials. A referral from a trusted source can significantly increase the chances of winning over a big client.12. Provide Proactive Support and Continuous Improvement:To maintain a successful relationship with big clients, it is important to provide proactive support and continuously seek waysto improve the value you offer. Regularly communicate with the client to address any concerns or issues, and proactively offer suggestions on how to optimize their use of your product or service. This level of attentiveness and ongoing improvement shows the client that you are committed to their success and are invested in their long-term satisfaction.13. Offer Competitive Pricing and Terms:Pricing plays a crucial role when selling to big clients. It is important to offer competitive pricing that aligns with the value you provide. Conduct a thorough analysis of the market and competitors to ensure your pricing is in line with industry standards. Additionally, be flexible with contract terms, such as payment schedules and delivery options, to accommodate the client's preferences. This will help position your organization as a trusted partner that is willing to work with the client to meet their unique needs.14. Develop a Long-term Account Management Strategy: Winning a big client is just the first step; maintaining and growing the relationship over time is equally important. Develop a long-term account management strategy that focuses on nurturing the relationship, providing ongoing support, and identifying opportunities for upselling or cross-selling. Regularly review and assess the client's evolving needs and goals, and proactively offer solutions that can help them achieve continuous improvement and success.Selling to big clients requires a well-thought-out strategy, a deep understanding of the client's needs, excellent customer service, andcontinuous commitment to delivering value. By implementing these strategies, sales teams can enhance their chances of winning and maintaining relationships with big clients, which can significantly contribute to the growth and success of the organization.。

siRNA非病毒载体递送用于肿瘤治疗的研究进展

第４２卷㊀第５期２０２３年㊀１０月北京生物医学工程ＢｅｉｊｉｎｇＢｉｏｍｅｄｉｃａｌＥｎｇｉｎｅｅｒｉｎｇＶｏｌ４２㊀Ｎｏ５Ｏｃｔｏｂｅｒ㊀２０２３㊃综㊀述㊃作者单位：１㊀上海理工大学健康科学与工程学院（上海㊀２０００９３）２㊀上海健康医学院（上海㊀２０１３１８）通信作者：朱君，Ｅ⁃ｍａｉｌ：ｙｚｊｚｈｕ＠１６３ｃｏｍ；李伟，Ｅ⁃ｍａｉｌ：４１０４１６８２７＠ｑｑｃｏｍｓｉＲＮＡ非病毒载体递送用于肿瘤治疗的研究进展王飞１㊀严辰玥２㊀孙嘉２㊀商宇萌２㊀李伟２㊀朱君２摘㊀要㊀近年来基于ＲＮＡ干扰（ＲＮＡｉｎｔｅｒｆｅｒｅｎｃｅ，ＲＮＡｉ）的基因治疗技术在肿瘤治疗方面引起广泛关注㊂在常规药物治疗无效的情况下，ＲＮＡｉ为癌症患者带来了新的希望㊂但是，由于小分子干扰ＲＮＡ（ｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡ，ｓｉＲＮＡ）在体内存在易降解㊁难递送等问题，极大地限制了其临床转化潜力㊂纳米载体以其独特的尺寸效应和多样的修饰策略，能够介导高效㊁靶向的ＲＮＡ递送，以实现其基因沉默㊂本文综述了ＲＮＡｉ在基因治疗中的作用机制以及体内递送ｓｉＲＮＡ的不同载体，介绍了载体体内递送ｓｉＲＮＡ的主要障碍和作用靶点，并比较了不同载体在ｓｉＲＮＡ递送中的优势和不足，为新载体的设计提供借鉴，推动ＲＮＡ干扰疗法向临床的转化㊂关键词㊀ＲＮＡ干扰；小分子干扰ＲＮＡ；基因沉默；纳米载体；肿瘤治疗ＤＯＩ：１０３９６９／ｊ．ｉｓｓｎ．１００２－３２０８２０２３０５０１８．中图分类号㊀Ｒ３１８０４㊀㊀文献标志码㊀Ａ㊀㊀文章编号㊀１００２－３２０８（２０２３）０５－０５４１－０５本文著录格式㊀王飞，严辰玥，孙嘉，等．ｓｉＲＮＡ非病毒载体递送用于肿瘤治疗的研究进展［Ｊ］．北京生物医学工程，２０２３，４２（５）：５４１－５４５．ＷＡＮＧＦｅｉ，ＹＡＮＣｈｅｎｙｕｅ，ＳＵＮＪｉａ，ｅｔａｌ．Ｒｅｓｅａｒｃｈｐｒｏｇｒｅｓｓｏｆｎｏｎ⁃ｖｉｒａｌｄｅｌｉｖｅｒｙｏｆｓｉＲＮＡｆｏｒｔｕｍｏｒｔｈｅｒａｐｙ［Ｊ］．ＢｅｉｊｉｎｇＢｉｏｍｅｄｉｃａｌＥｎｇｉｎｅｅｒｉｎｇ，２０２３，４２（５）：５４１－５４５．Ｒｅｓｅａｒｃｈｐｒｏｇｒｅｓｓｏｆｎｏｎ⁃ｖｉｒａｌｄｅｌｉｖｅｒｙｏｆｓｉＲＮＡｆｏｒｔｕｍｏｒｔｈｅｒａｐｙＷＡＮＧＦｅｉ１，ＹＡＮＣｈｅｎｙｕｅ２，ＳＵＮＪｉａ２，ＳＨＡＮＧＹｕｍｅｎｇ２，ＬＩＷｅｉ２，ＺＨＵＪｕｎ２１㊀ＳｃｈｏｏｌｏｆＨｅａｌｔｈＳｃｉｅｎｃｅａｎｄＥｎｇｉｎｅｅｒｉｎｇ，ＵｎｉｖｅｒｓｉｔｙｏｆＳｈａｎｇｈａｉｆｏｒＳｃｉｅｎｃｅａｎｄＴｅｃｈｎｏｌｏｇｙ，Ｓｈａｎｇｈａｉ㊀２０００９３；２㊀ＳｈａｎｇｈａｉＵｎｉｖｅｒｓｉｔｙｏｆＭｅｄｉｃｉｎｅ＆ＨｅａｌｔｈＳｃｉｅｎｃｅｓ，Ｓｈａｎｇｈａｉ㊀２０１３１８Ｃｏｒｒｅｓｐｏｎｄｉｎｇａｕｔｈｏｒｓ：ＺＨＵＪｕｎ（Ｅ⁃ｍａｉｌ：ｙｚｊｚｈｕ＠１６３ｃｏｍ）；ＬＩＷｅｉ（Ｅ⁃ｍａｉｌ：４１０４１６８２７＠ｑｑｃｏｍ）ʌＡｂｓｔｒａｃｔɔ㊀Ｉｎｒｅｃｅｎｔｙｅａｒｓ，ｇｅｎｅｔｈｅｒａｐｙｂａｓｅｄｏｎＲＮＡｉｎｔｅｒｆｅｒｅｎｃｅ（ＲＮＡｉ）ｈａｓａｔｔｒａｃｔｅｄｗｉｄｅａｔｔｅｎｔｉｏｎｉｎｔｕｍｏｒｔｈｅｒａｐｙ．ＲＮＡｉｏｆｆｅｒｓｎｅｗｈｏｐｅｆｏｒｃａｎｃｅｒｐａｔｉｅｎｔｓｗｈｅｎｃｏｎｖｅｎｔｉｏｎａｌｄｒｕｇｔｒｅａｔｍｅｎｔｓａｒｅｉｎｅｆｆｅｃｔｉｖｅ．Ｈｏｗｅｖｅｒ，ｄｕｅｔｏｔｈｅｐｒｏｂｌｅｍｓｓｕｃｈａｓｅａｓｙｄｅｇｒａｄａｔｉｏｎａｎｄｄｉｆｆｉｃｕｌｔｄｅｌｉｖｅｒｙｏｆｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡ（ｓｉＲＮＡ）ｉｎｖｉｖｏ，ｉｔｓｃｌｉｎｉｃａｌｔｒａｎｓｆｏｒｍａｔｉｏｎｐｏｔｅｎｔｉａｌｉｓｇｒｅａｔｌｙｌｉｍｉｔｅｄ．Ｗｉｔｈｉｔｓｕｎｉｑｕｅｓｉｚｅｅｆｆｅｃｔａｎｄｖａｒｉｏｕｓｍｏｄｉｆｉｃａｔｉｏｎｓｔｒａｔｅｇｉｅｓ，ｎａｎｏ⁃ｃａｒｒｉｅｒｃａｎｍｅｄｉａｔｅｅｆｆｉｃｉｅｎｔａｎｄｔａｒｇｅｔｅｄＲＮＡｄｅｌｉｖｅｒｙｔｏａｃｈｉｅｖｅｇｅｎｅｓｉｌｅｎｃｉｎｇ．ＴｈｉｓｐａｐｅｒｒｅｖｉｅｗｓｔｈｅｍｅｃｈａｎｉｓｍｏｆＲＮＡｉｉｎｇｅｎｅｔｈｅｒａｐｙａｎｄｄｉｆｆｅｒｅｎｔｃａｒｒｉｅｒｓｆｏｒｄｅｌｉｖｅｒｉｎｇｓｉＲＮＡｉｎｖｉｖｏ，ｉｎｔｒｏｄｕｃｅｓｔｈｅｍａｉｎｏｂｓｔａｃｌｅｓａｎｄｔａｒｇｅｔｓｏｆｓｉＲＮＡｄｅｌｉｖｅｒｙｉｎｖｉｖｏ，ａｎｄｃｏｍｐａｒｅｓｔｈｅａｄｖａｎｔａｇｅｓａｎｄｄｉｓａｄｖａｎｔａｇｅｓｏｆｄｉｆｆｅｒｅｎｔｃａｒｒｉｅｒｓｉｎｓｉＲＮＡｄｅｌｉｖｅｒｙ，ｓｏａｓｔｏｐｒｏｖｉｄｅｒｅｆｅｒｅｎｃｅｆｏｒｔｈｅｄｅｓｉｇｎｏｆｎｅｗｖｅｃｔｏｒｓａｎｄｐｒｏｍｏｔｅｔｈｅｔｒａｎｓｆｏｒｍａｔｉｏｎｏｆＲＮＡｉｔｈｅｒａｐｙｔｏｃｌｉｎｉｃ．ʌＫｅｙｗｏｒｄｓɔ㊀ＲＮＡｉｎｔｅｒｆｅｒｅｎｃｅ；ｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡ；ｇｅｎｅｓｉｌｅｎｃｉｎｇ；ｎａｎｏ⁃ｃａｒｒｉｅｒ；ｔｕｍｏｒｔｈｅｒａｐｙ０㊀引言癌症是全球死亡率最高的非传染性疾病之一，已经成为人类生命健康的主要威胁［１］㊂通过手术㊁放化疗等传统方法治疗癌症通常费用昂贵，且患者痛苦，有时甚至效率低下㊂癌症的基因治疗具有疗效高㊁副作用小等优点［２］㊂其中ＲＮＡｉ是一种是将非编码双链ＲＮＡ（ｄｏｕｂｌｅ⁃ｓｔｒａｎｄｅｄＲＮＡ，ｄｓＲＮＡ）送入癌细胞，引发靶向信使ＲＮＡ（ｍｅｓｓｅｎｇｅｒＲＮＡ，ｍＲＮＡ）的同源依赖性降解，从而导致特异性的基因沉默机制［３－４］㊂由ｄｓＲＮＡ引起的基因沉默现象最早在植物中观察到，其中ｓｉＲＮＡ是一种可以沉默靶基因表达，具有特定序列和长度（２１２３个碱基对）的ｄｓＲＮＡ分子㊂它可以由ｄｓＲＮＡ经Ｄｉｃｅｒ酶裂解后在胞内生成，也可以通过人工合成㊂进入胞浆后的ｓｉＲＮＡ与Ａｇｏ蛋白形成ＲＮＡ诱导的沉默复合物（ＲＮＡ⁃ｉｎｄｕｃｅｄｓｉｌｅｎｃｉｎｇｃｏｍｐｌｅｘ，ＲＩＳＣ）㊂在ＲＩＳＣ中ｓｉＲＮＡ裂解，随后由反义链对靶ｍＲＮＡ进行碱基配对酶切，抑制了目标ＲＮＡ翻译为蛋白质，达到基因沉默的目的［５－６］㊂ＦＤＡ批准Ａｌｎｙｌａｍ生产的ＯＮＰＡＴＴＲＯ投入临床治疗［７］，标志着ＲＮＡ成为继化学和蛋白质疗法之后在制药学的第三个里程碑㊂目前ｓｉＲＮＡ非病毒载体递送用于肿瘤治疗已成为纳米生物医药的研究热点㊂ｓｉＲＮＡ可以通过诱导ｍＲＮＡ的降解，以序列特异性的方式抑制致癌基因的表达，在细胞信号转导中发挥重要作用，因此基于ｓｉＲＮＡ的抗癌药物具有广泛的应用前景㊂但是目前ｓｉＲＮＡ递送的主要障碍有：全身给药后ｓｉＲＮＡ在体内的非特异性分布造成的低转染效率，引起免疫反应及毒性；ｓｉＲＮＡ易受核酸酶的降解以及网状内皮系统的清除；血管内皮壁㊁多重组织的物理屏障阻碍了ｓｉＲＮＡ药物导入肿瘤细胞；ｓｉＲＮＡ被细胞摄取和内吞效应低；ｓｉＲＮＡ无法实现高效的内体逃逸以及其对ｍＲＮＡ的脱靶效应㊂为了克服这些问题，本文将围绕ｓｉＲＮＡ非病毒载体进行综述，主要包括载体的体内递送过程㊁不同载体用于ｓｉＲＮＡ递送中的优势和不足，以及它们中一些已经进入临床试验的ｓｉＲＮＡ载体及制剂，为新载体的设计提供借鉴，推动ＲＮＡｉ疗法向临床的转化㊂１㊀ｓｉＲＮＡ药物用于治疗的主要障碍及作用靶点㊀㊀通过化学修饰和特定序列设计的ＲＮＡｉ疗法几乎能够降解任何基因ｍＲＮＡ转录物，具有高度特异性㊂同时它依赖ＡＴＰ的供能，通过天然的调节途径，以催化作用的方式将抑制特定基因表达的效率最大化㊂选择合适的靶点和给药途径非常重要㊂ｓｉＲＮＡ在消化道内的不稳定性以及其对于肠道上皮细胞的低渗透性都严重阻碍了口服给药的进行㊂同时皮下注射也受到亲脂性和载体大小的限制㊂相比之下，静脉注射是首选㊂静脉注射后裸露的ｓｉＲＮＡ分子会被血清核酸内切酶降解，最终被肾脏清除［８］㊂同时网状内皮系统（如肝㊁脾）巨噬细胞的非特异性摄取也会对它们造成吞噬破坏㊂在细胞外屏障方面，细胞外基质的复杂性㊁ｓｉＲＮＡ与细胞膜之间的电荷排斥以及选择性区域（如血脑屏障）的紧密连接都阻碍ｓｉＲＮＡ对组织的渗透［９－１０］㊂在细胞内屏障中，通过内吞作用进入胞内的ｓｉＲＮＡ分子如果无法实现早期的内体逃逸，则会被溶酶体酸化降解以及胞吐排出［１１］㊂逃逸到细胞质中的外源性ｓｉＲＮＡ还可能会造成靶基因以外的基因表达减少，具有潜在治疗风险㊂此外，ｓｉＲＮＡ序列中的特殊结构可能会通过激活Ｔｏｌｌ样受体，产生干扰素（α或β）和炎性细胞因子，触发不必要的免疫反应㊂针对药物和抗体难以抑制的转录因子和某些关键的肿瘤蛋白（如Ｒａｓ）［１２］，ｓｉＲＮＡ可以通过碱基配对识别其靶标㊂目前已有多种靶点被开发出来用于抗肿瘤药物的筛选，包括程序性死亡因子配体－１（ｐｒｏｇｒａｍｍｅｄｄｅａｔｈｌｉｇａｎｄ１，ＰＤ－Ｌ１）㊁细胞毒性Ｔ淋巴细胞相关蛋白４（ｃｙｔｏｔｏｘｉｃＴ－ｌｙｍｐｈｏｃｙｔｅ⁃ａｓｓｏｃｉａｔｅｄｐｒｏｔｅｉｎ４，ＣＴＬＡ４）㊁表皮生长因子受体（ｅｐｉｄｅｒｍａｌｇｒｏｗｔｈｆａｃｔｏｒｒｅｃｅｐｔｏｒ，ＥＧＦＲ）㊁血管内皮生长因子等㊂根据靶标作用机制可以将其分为靶向肿瘤形成调控机制㊁肿瘤微环境㊁肿瘤免疫调节㊁肿瘤生物标志物及肿瘤干细胞㊂ＥＧＦＲ常在非小细胞肺癌中表达异常，其中１９号外显因子缺失突变最为常见㊂它激活了ＥＧＦＲ的酪氨酸激酶活性，从而诱导下游的促生长信号通路㊂Ｎａｓｃｉｍｅｎｔｏ等［１３］将构建的针对致癌ＥＧＦＲ突变体的等位基因特异性ｓｉＲＮＡ递送到肺肿瘤模型中，成功诱导了其凋亡㊂针对ＰＤ－Ｌ１和ＣＴＬＡ４的免疫疗法已经在治疗黑色素瘤㊁霍奇金淋巴瘤㊁非小细胞肺癌和膀胱癌中获得了进展㊂２㊀ｓｉＲＮＡ递送载体的主要类型开发合适的载体显得非常必要㊂目前研究主要集中在开发保护ｓｉＲＮＡ不受核酸酶影响的载体㊂载体通常以静电或共价方式［１４］与ｓｉＲＮＡ结合形成纳米颗粒㊂㊃２４５㊃北京生物医学工程㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀第４２卷２１㊀脂质体及脂质类似物脂质体制剂具有高度的生物相容性，作为最成熟的ＲＮＡ载体已成功应用于ＣＯＶＩＤ－１９ｍＲＮＡ疫苗的递送，推动了基因治疗的边界㊂脂质体中阳离子脂类最常见，它通过静电吸附的方式显著提高了体外转染效率㊂目前大多数脂质复合物在阳离子脂类的基础上添加了如二油酰磷脂酰胆碱（ｄｉｏｌｅｏｙｌｐｈｏｓｐｈａｔｉｄｙｌｃｈｏｌｉｎｅ，ＤＯＰＣ）㊁二油酰磷脂酰乙醇胺（ｄｉｏｌｅｏｙｌｐｈｏｓｐｈａｔｉｄｙｌｅｔｈａｎｏｌａｍｉｎｅ，ＤＯＰＥ）㊁胆固醇［１５］和其他一些天然脂类㊂这些中性辅助脂质提高了载体的稳定性和细胞摄取率㊂Ｈａｔｔｏｒｉ等［１６］制备了１７种由阳离子脂质和ＤＯＰＥ组成的脂质复合物，结果表明不同的阳离子脂质类型对静脉注射后ｓｉＲＮＡ的生物分布和抑制效率影响显著㊂相比之下，环境响应型脂质是一类新型的脂质传递系统㊂这些脂质具有简单的化学结构，并对肿瘤微环境的变化作出响应（如可电离且ｐＨ敏感的可质子化氨基脂）㊂与阳离子脂质不同，可质子化氨基脂中的氨基头基在酸性ｐＨ下会电离而带强正电荷，电荷密度控制着颗粒之间的相互作用并抗衡离子的吸附，从而控制着纳米颗粒的稳定性㊂多项研究表明肿瘤微环境响应型脂质疗效高且副作用低，但其在克服免疫系统的清除实现最大递送效率方面还需进一步优化㊂临床上脂质体制剂Ａｔｕ０２７和ＡＬＮ－ＶＳＰ０２已经分别完成了Ⅰ／Ⅱ期和Ⅰ期试验㊂其中Ａｔｕ０２７是一种针对蛋白激酶Ｎ３的特异性ｓｉＲＮＡ制剂，它联合吉西他滨在治疗晚期胰腺癌受试者上显示出良好的安全性和耐受性㊂同时Ｔｅｋｍｉｒａ公司研发出一款靶向于Ｐｏｌｏ样激酶１的ｓｉＲＮＡ药物ＴＫＭ－０８０３０１㊂针对该药物开展的Ⅰ／Ⅱ期临床研究在晚期实体瘤患者中进行，结果证明了它的抗肿瘤活性和良好耐受性㊂２２㊀聚合物聚合物容易大规模合成与生产，且其只依赖于非共价作用，如静电效应或氢键压缩ｓｉＲＮＡ㊂目前多种阳离子聚合物（ｃａｔｉｏｎｉｃｐｏｌｙｍｅｒ，ＣＰ）已被广泛用于核酸传递，它们具有共同的理化特性［１７］，如阳离子电荷㊁两亲性和融合性㊂具有代表性的ＣＰ有聚乙烯亚胺（ｐｏｌｙｅｔｈｙｌｅｎｉｍｉｎｅ，ＰＥＩ）㊁聚β－氨基酸酯（Ｐｏｌｙβ－ａｍｉｎｅｓｔｅｒｓ，ＰＢＡＥ）㊁聚赖氨酸（ｐｏｌｙ⁃Ｌ⁃ｌｙｓｉｎｅ，ＰＬＬ）㊁聚丙交酯乙交酯（ｐｏｌｙｌａｃｔｉｄｅ⁃ｃｏ⁃ｇｌｙｃｏｌｉｄｅ，ＰＬＧＡ）以及聚酰胺胺（ｐｏｌｙａｍｉｄｏａｍｉｎｅ，ＰＡＭＡＭ）等㊂ＣＰ方便进行化学修饰，与阳离子脂质体相比它不含疏水部分而直接溶于水㊂目前ＣＰ的转染效率和细胞毒性之间的平衡问题是其用于临床的主要挑战㊂聚乙烯亚胺（Ｐｏｌｙｅｔｈｙｌｅｎｅｉｍｉｎｅ，ＰＥＩ）可将外源基因转染到悬浮细胞或贴壁细胞中㊂它的高缓冲能力可以通过质子海绵效应促进内体释放［１８］㊂然而ＰＥＩ通常不易降解，聚合链上的高密度电荷与蛋白质之间的强烈作用也会降低多聚体的血清稳定性㊂Ｘｕｅ等［１９］通过三氟乙酸乙酯和全氟丁酰氯的酰胺化反应合成的两个系列的氟化ＰＥＩ，发现经氟化处理后的ＰＥＩ细胞毒性显著降低㊂氟化已被证明是降低ＰＥＩ的细胞毒性和提高ｓｉＲＮＡ递送效率的有效方法㊂ＰＬＬ和ＰＢＡＥ与ＰＥＩ相比生物相容性更好，但是化学键的不稳定性增加了它们进行高效递送的难度［２０］㊂ＰＬＧＡ具有粒径小㊁相对无毒和持续释放轮廓的优点㊂表面具有大量活性基团的ＰＡＭＡＭ树枝状大分子可以通过修饰不同的官能团（配体）来实现其药物靶向［２１］㊂然而高度分支化的ＰＡＭＡＭ提供了高效基因转染的同时也具有高度毒性㊂不同于线型结构的ＣＰ，分支化的ＣＰ通过其多功能末端基团组成的三维结构能更紧密地包裹ｓｉＲＮＡ，在生理ｐＨ下形成多聚复合物㊂与ＣＰ相比，天然类聚合物生物相容性更好㊂胶原蛋白是天然类聚合物的代表㊂目前试验中常通过靶向修饰ｓｉＲＮＡ／胶原蛋白复合物来抑制肿瘤生长㊂基于环糊精聚合物的纳米颗粒ＣＡＬＡＡ－０１是第一个进入癌症临床试验的靶向ｓｉＲＮＡ传递系统［２２］，但是Ⅰ期临床试验由于患者出现剂量限制的毒副反应而终止㊂壳聚糖（ｃｈｉｔｏｓａｎ，ＣＳ）是一种线性多糖，ｐＫａ值为６２７０的Ｄ－氨基葡萄糖残基弱化了壳聚糖的碱性㊂当ｐＨ低于ｐＫａ时，伯胺会质子化㊂ＣＳ与ｓｉＲＮＡ结合构成的磷酸骨架转染效率较低㊂Ｃｈｏｉ等［２３］通过加入阳离子谷氨酰胺偶联壳寡糖构建了纳米载体系统，显著提高了转染效率㊂在治疗胰腺癌方面，以聚合物胶束为制剂的ＮＣ－６００４已经进入到Ⅲ期临床试验㊂而ＮＣ－４０１６也投入到治疗各种实体瘤初步的临床药理学㊁人体安全性评价试验中㊂同时，ＳｉｌｅｎＳｅｅｄ公司研发出的靶向ｓｉＲＮＡ药物ｓｉＧ１２Ｄ－ＬＯＤＥＲ也进入Ⅱ期临床试验㊂它是一种可生物降解的聚合物基质，其Ⅰ期数据显示出与化疗药物（如吉西他滨㊁厄洛替尼以及奥沙利铂）联用对胰腺导管腺癌具有一定疗效㊂㊃３４５㊃第５期㊀㊀㊀㊀㊀㊀王飞，等：ｓｉＲＮＡ非病毒载体递送用于肿瘤治疗的研究进展２３㊀无机纳米颗粒无机纳米粒子（ｉｎｏｒｇａｎｉｃｎａｎｏｐａｒｔｉｃｌｅｓ，ＩＮＰｓ）尺寸可控㊁表面易于化学修饰，显示出对酶降解优异稳定性的同时体内示踪效果也较好㊂目前主要需要克服其在体内长期滞留带来的潜在不良反应㊂常用的ＩＮＰｓ如下：金纳米颗粒（ｇｏｌｄｎａｎｏｐａｒｔｉｃｌｅｓ，ＧＮＰｓ）的尺寸很小，能够直接通过核孔复合体进行核靶向㊂此外，ＧＮＰｓ通过改变不同的生物活性配体如肽㊁聚合物和抗体来实现其功能多样性㊂据报道，环状精甘天冬氨酸（ａｒｇｉｎｙｌｇｌｙｃｙｌａｓｐａｒｔｉｃａｃｉｄ，ＲＧＤ）肽修饰的ＧＮＰｓ抗癌效果良好㊂相对于Ｃｕ和Ａｇ，Ｓ与Ａｕ配体的共价性较强㊂利用ＧＮＰｓ传递ｓｉＲＮＡ的最直接方法是通过Ａｕ－Ｓ共价将ｓｉＲＮＡ偶联到其表面㊂例如，Ａｈｗａｚｉ等［２４］将人类免疫缺陷病毒的反式激活蛋白通过Ａｕ－Ｓ键偶联到ＧＮＰｓ上来治疗乳腺癌㊂磁性氧化铁纳米颗粒通过磁响应性在控制粒子目标成像的同时还能产生高热来消融组织㊂介孔二氧化硅纳米颗粒（ｍｅｓｏｐｏｒｏｕｓｓｉｌｉｃａｎａｎｏｐａｒｔｉｃｌｅｓ，ＭＳＮｓ）比表面积大，结合位点多，易于官能化㊂Ｐｉｎｅｓｅ等［２５］将ＰＥＩ接枝到粒子的表面，设计了一种纤维表面吸附的新型ｓｉＲＮＡ／ＭＳＮ－ＰＥＩ涂层支架，基因沉默效果良好㊂目前已证明用阳离子聚合物包覆的ＭＳＮｓ可以有效地负载ｓｉＲＮＡ㊂最近，一种用于正电子发射断层扫描光学成像的１２４Ｉ环状ＲＧＤ多肽无机杂化纳米粒子由于其尺寸极小㊁靶向性好而受到了关注㊂它在Ⅰ期临床试验中对转移性黑色素瘤的整合表达病灶产生了明显的对比㊂２４㊀细胞穿透肽细胞穿透肽（ｃｅｌｌ⁃ｐｅｎｅｔｒａｔｉｎｇｐｅｐｔｉｄｅｓ，ＣＰＰ）因病毒跨膜蛋白结构域的研究而被发现［２６］㊂在增强ＣＰＰ靶向特异性方面主要有两种方法：设计以肿瘤细胞为首选和针对癌细胞内特性的工程肽㊂药物可以与肿瘤归巢蛋白㊁膜受体特异性抗体相连接㊂此外，基于ＣＰＰ的药物可以被设计成只在肿瘤特殊的生理微环境中激活㊂如Ｂｅｎ等［２７］通过研究由细胞穿透肽ｇＨ６２５功能化的ｓｉＲＮＡ纳米载体（称为ＣＳ⁃ＭＳＮ）在三阴性乳腺癌模型中的细胞转运，发现ＣＳ⁃ＭＳＮ转染效率比相同的不含ｇＨ６２５肽的纳米载体高１７倍㊂同人工合成载体的内吞作用不同，ＣＰＰ最大的特征在于其可以不依赖能量直接穿膜㊂ＣＰＰ与ｓｉＲＮＡ共价或非共价结合成纳米颗粒，但其在体内递送的稳定性还有待提高㊂２５㊀外泌体外泌体具有长循环的半衰期和可变形的细胞骨架，它在细胞间充当着通信媒介的作用㊂同时部分细胞分泌的外泌体对肿瘤还具有归巢能力［２８］㊂Ｘｕ等［２９］以Ｐ２１激活激酶（４Ｐ２１－ａｃｔｉｖａｔｅｄｋｉｎａｓｅ４，ＰＡＫ４）为靶点，通过瘤内注射将来自胰腺癌的外泌体包裹ＰＡＫ４特异性ｓｉＲＮＡ（ＰＡＫ４－ｓｐｅｃｉｆｉｃｓｉＲＮＡ，ｓｉＰＡＫ４）输送到肿瘤细胞中，Ｈ＆Ｅ染色显示ｓｉＰＡＫ４处理组有明显的组织细胞凋亡，小鼠的存活率显著提高（Ｐ＜０００１）㊂外泌体具有和脂质体类似的双层磷脂，膜上特定的蛋白与脂质有助于其靶向融合㊂但与人工合成脂质不同，细胞自身分泌的膜囊泡可以最大限度地降低机体的免疫反应㊂目前提高外泌体的ＲＮＡ装载量是需要解决的首要问题㊂３㊀结语ｓｉＲＮＡ是一种可以下调那些直接或间接导致癌细胞异常增殖基因的有效工具［３０］㊂本文综述了各种递送载体用于肿瘤治疗的现状㊂传统的阳离子脂质和聚合物转染效率高㊁生产简单，但还存在高电荷引起的潜在毒性㊁靶向能力弱㊁难以在体内追踪等问题㊂新型环境响应型脂质是一种具有明确㊁简单化学结构的载体㊂在临床上，脂质体（如阿霉素脂质体）是第一类获得ＦＤＡ批准用于治疗癌症的纳米颗粒［３１］㊂与聚合物和脂质体相比，尺寸可控的ＩＮＰｓ更加稳定㊂ＩＮＰｓ由于其独特的物理化学性质便于体内示踪，然而它们的生物安全性还有待进一步检验㊂目前已有大量ＣＰＰ成功实现了体外细胞对ｓｉＲＮＡ的高效转染，细胞毒性小，但是它在体内并不稳定㊂而外泌体生物相容性好，前景广阔㊂理想的ｓｉＲＮＡ递送系统应该是无毒且非免疫原性的，以保护ｓｉＲＮＡ在递送过程中不被降解，并促进肿瘤组织的特异性高效摄取㊂相信随着纳米载药技术的不断发展，在不久的将来，基于基因突变的个性化治疗将成为可能㊂参考文献［１］㊀ＳｉｇｅｌＲＬ，ＭｉｌｌｅｒＫＤ，ＦｕｃｈｓＨＥ，ｅｔａｌ．Ｃａｎｃｅｒｓｔａｔｉｓｔｉｃｓ，２０２１［Ｊ］．ＣＡ：ＡＣａｎｃｅｒＪｏｕｒｎａｌｆｏｒＣｌｉｎｉｃｉａｎｓ，２０２１，７１（１）：７－３３．［２］㊀ＴａｎｇＹ，ＬｉｕＹ，ＸｉｅＹＷ，ｅｔａｌ．ＡｐｏｐｔｏｓｉｓｏｆＡ５４９ｃｅｌｌｓｂｙｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡｔａｒｇｅｔｉｎｇｓｕｒｖｉｖｉｎｄｅｌｉｖｅｒｙｕｓｉｎｇｐｏｌｙ－β－ａｍｉｎｏｅｓｔｅｒ／ｇｕａｎｉｄｉｎｙｌａｔｅｄＯ⁃ｃａｒｂｏｘｙｍｅｔｈｙｌｃｈｉｔｏｓａｎｎａｎｏｐａｒｔｉｃｌｅｓ［Ｊ］．ＡｓｉａｎＪｏｕｒｎａｌｏｆＰｈａｒｍａｃｅｕｔｉｃａｌＳｃｉｅｎｃｅｓ，２０２０，１５（１）：１２１－１２８．㊃４４５㊃北京生物医学工程㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀㊀第４２卷［３］㊀ＣｏｎｄｅＪ，ＡｍｂｒｏｓｏｎｅＡ，ＨｅｒｎａｎｄｅｚＹ，ｅｔａｌ．１５ｙｅａｒｓｏｎｓｉＲＮＡｄｅｌｉｖｅｒｙ：ＢｅｙｏｎｄｔｈｅＳｔａｔｅ⁃ｏｆ⁃ｔｈｅ⁃ＡｒｔｏｎｉｎｏｒｇａｎｉｃｎａｎｏｐａｒｔｉｃｌｅｓｆｏｒＲＮＡｉｔｈｅｒａｐｅｕｔｉｃｓ［Ｊ］．ＮａｎｏＴｏｄａｙ，２０１５，１０（４）：４２１－４５０．［４］㊀ＨａｔｔａｂＤ，ＢａｋｈｔｉａｒＡ．ＢｉｏｅｎｇｉｎｅｅｒｅｄｓｉＲＮＡ⁃Ｂａｓｅｄｎａｎｏｐｌａｔｆｏｒｍｓｔａｒｇｅｔｉｎｇｍｏｌｅｃｕｌａｒｓｉｇｎａｌｉｎｇｐａｔｈｗａｙｓｆｏｒｔｈｅｔｒｅａｔｍｅｎｔｏｆｔｒｉｐｌｅｎｅｇａｔｉｖｅｂｒｅａｓｔｃａｎｃｅｒ：ｐｒｅｃｌｉｎｉｃａｌａｎｄｃｌｉｎｉｃａｌａｄｖａｎｃｅｍｅｎｔｓ［Ｊ］．Ｐｈａｒｍａｃｅｕｔｉｃｓ，２０２０，１２（１０）：９２９．［５］㊀黄林卓，蔡佩娥，尹东，等．肿瘤微环境响应的纳米载体用于ｓｉＲＮＡ体内递送研究进展［Ｊ］．中国科学：生命科学，２０２０，５０（１０）：１０８２－１１０２．ＨｕａｎｇＬＺ，ＣａｉＰＥ，ＹｉｎＤ，ｅｔａｌ．Ｐｒｏｇｒｅｓｓｉｎｔｈｅｔｕｍｏｒｅｎｖｉｒｏｎｍｅｎｔ⁃ｒｅｓｐｏｎｓｉｖｅｎａｎｏｃａｒｒｉｅｒｓｆｏｒｉｎｖｉｖｏｓｉＲＮＡｄｅｌｉｖｅｒｙ［Ｊ］．ＳＣＩＥＮＣＥＣＨＩＮＡ：ＬｉｆｅＳｃｉｅｎｃｅｓ，２０２０，５０（１０）：１０８２－１１０２．［６］㊀ＳｈｉＪＪ，ＫａｎｔｏｆｆＰＷ，ＷｏｏｓｔｅｒＲ，ｅｔａｌ．Ｃａｎｃｅｒｎａｎｏｍｅｄｉｃｉｎｅ：ｐｒｏｇｒｅｓｓ，ｃｈａｌｌｅｎｇｅｓａｎｄｏｐｐｏｒｔｕｎｉｔｉｅｓ．［Ｊ］．ＮａｔｕｒｅＲｅｖｉｅｗｓＣａｎｃｅｒ，２０１７，１７（１）：２０－３７．［７］㊀ＢｉｎｚｅｌＤＷ，ＧｕｏＳＣ，ＹｉｎＨＲ，ｅｔａｌ．Ｒａｔｉｏｎａｌｄｅｓｉｇｎｆｏｒｃｏｎｔｒｏｌｌｅｄｒｅｌｅａｓｅｏｆｄｉｃｅｒ⁃ｓｕｂｓｔｒａｔｅｓｉＲＮＡｈａｒｂｏｒｅｄｉｎｐｈｉ２９ｐＲＮＡ⁃ｂａｓｅｄｎａｎｏｐａｒｔｉｃｌｅｓ［Ｊ］．ＭｏｌｅｃｕｌａｒＴｈｅｒａｐｙ⁃ＮｕｃｌｅｉｃＡｃｉｄｓ，２０２１，２５：５２４－５３５．［８］㊀ＣｈａｒｂｅＮＢ，ＡｍｎｅｒｋａｒＮＤ，ＲａｍｅｓｈＢ，ｅｔａｌ．ＳｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡｆｏｒｃａｎｃｅｒｔｒｅａｔｍｅｎｔ：ｏｖｅｒｃｏｍｉｎｇｈｕｒｄｌｅｓｉｎｄｅｌｉｖｅｒｙ．［Ｊ］．ＡｃｔａＰｈａｒｍａｃｅｕｔｉｃａＳｉｎｉｃａ．Ｂ，２０２０，１０（１１）：２０７５－２１０９．［９］㊀ＷａｎｇＪＪ，ＷａｎｇＹＣ，ＷａｎｇＲＦ，ｅｔａｌ．Ｔａｒｇｅｔｅｄｎａｎｏｐａｒｔｉｃｌｅｓｆｏｒｐｒｅｃｉｓｅｃａｎｃｅｒｔｈｅｒａｐｙ［Ｊ］．ＳｃｉｅｎｃｅＣｈｉｎａＬｉｆｅＳｃｉｅｎｃｅｓ，２０１９，６２（１０）：１３９２－１３９５．［１０］㊀ＬｉｕＹ，ＸｕＣＦ，ＩｑｂａｌＳ，ｅｔａｌ．Ｒｅｓｐｏｎｓｉｖｅｎａｎｏｃａｒｒｉｅｒｓａｓａｎｅｍｅｒｇｉｎｇｐｌａｔｆｏｒｍｆｏｒｃａｓｃａｄｅｄｄｅｌｉｖｅｒｙｏｆｎｕｃｌｅｉｃａｃｉｄｓｔｏｃａｎｃｅｒ［Ｊ］．ＡｄｖａｎｃｅｄＤｒｕｇＤｅｌｉｖｅｒｙＲｅｖｉｅｗｓ，２０１７，１１５：９８－１１４．［１１］㊀ＫｉｍＢ，ＰａｒｋＪＨ，ＳａｉｌｏｒＭＪ．ＲｅｋｉｎｄｌｉｎｇＲＮＡｉｔｈｅｒａｐｙ：ｍａｔｅｒｉａｌｓｄｅｓｉｇｎｒｅｑｕｉｒｅｍｅｎｔｓｆｏｒｉｎｖｉｖｏｓｉＲＮＡｄｅｌｉｖｅｒｙ［Ｊ］．ＡｄｖａｎｃｅｄＭａｔｅｒｉａｌｓ，２０１９，３１（４９）：１９０３６３７．［１２］㊀ＲａｎｋＡＰ，ＫｏｃｈＡ．Ｌａｂ⁃ｔｏ⁃ｆｉｅｌｄｔｒａｎｓｉｔｉｏｎｏｆｒｎａｓｐｒａｙａｐｐｌｉｃａｔｉｏｎｓ⁃Ｈｏｗｆａｒａｒｅｗｅ？［Ｊ］．ＦｒｏｎｔｉｅｒｓｉｎＰｌａｎｔＳｃｉｅｎｃｅ，２０２１，１２：７５５２０３．［１３］㊀ＮａｓｃｉｍｅｎｔｏＡＶ，ＳｉｎｇｈＡ，ＢｏｕｓｂａａＨ，ｅｔａｌ．Ｏｖｅｒｃｏｍｉｎｇｃｉｓｐｌａｔｉｎｒｅｓｉｓｔａｎｃｅｉｎｎｏｎ⁃ｓｍａｌｌｃｅｌｌｌｕｎｇｃａｎｃｅｒｗｉｔｈＭａｄ２ｓｉｌｅｎｃｉｎｇｓｉＲＮＡｄｅｌｉｖｅｒｅｄｓｙｓｔｅｍｉｃａｌｌｙｕｓｉｎｇＥＧＦＲ⁃ｔａｒｇｅｔｅｄｃｈｉｔｏｓａｎｎａｎｏｐａｒｔｉｃｌｅｓ［Ｊ］．ＡｃｔａＢｉｏｍａｔｅｒｉａｌｉａ，２０１７，４７：７１－８０．［１４］㊀ＡｌｓｈａｅｒＷ，ＺｕｒｅｉｇａｔＨ，ＡＩＫａｒａｋｉＡ，ｅｔａｌ．ｓｉＲＮＡ：Ｍｅｃｈａｎｉｓｍｏｆａｃｔｉｏｎ，ｃｈａｌｌｅｎｇｅｓ，ａｎｄｔｈｅｒａｐｅｕｔｉｃａｐｐｒｏａｃｈｅｓ［Ｊ］．ＥｕｒｏｐｅａｎＪｏｕｒｎａｌｏｆＰｈａｒｍａｃｏｌｏｇｙ，２０２１，９０５：１７４１７８．［１５］㊀ＡｎｔｉｐｉｎａＡＹ，ＧｕｒｔｏｖｅｎｋｏＡＡ．Ｔｏｗａｒｄｕｎｄｅｒｓｔａｎｄｉｎｇｌｉｐｏｓｏｍｅ⁃ｂａｓｅｄｓｉＲＮＡｄｅｌｉｖｅｒｙｖｅｃｔｏｒｓ：ａｔｏｍｉｃ⁃ｓｃａｌｅｉｎｓｉｇｈｔｉｎｔｏｓｉＲＮＡ⁃ｌｉｐｉｄｉｎｔｅｒａｃｔｉｏｎｓ［Ｊ］．Ｌａｎｇｍｕｉｒ，２０１８，３４（２９）：８６８５－８６９３．［１６］㊀ＨａｔｔｏｒｉＹ，ＮａｋａｍｕｒａＭ，ＴａｋｅｕｃｈｉＮ，ｅｔａｌ．ＥｆｆｅｃｔｏｆｃａｔｉｏｎｉｃｌｉｐｉｄｉｎｃａｔｉｏｎｉｃｌｉｐｏｓｏｍｅｓｏｎｓｉＲＮＡｄｅｌｉｖｅｒｙｉｎｔｏｔｈｅｌｕｎｇｂｙｉｎｔｒａｖｅｎｏｕｓｉｎｊｅｃｔｉｏｎｏｆｃａｔｉｏｎｉｃｌｉｐｏｐｌｅｘ［Ｊ］．ＪｏｕｒｎａｌｏｆＤｒｕｇＴａｒｇｅｔｉｎｇ，２０１９，２７（２）：２１７－２２７．［１７］㊀ＷａｎｇＨ，ＭｉａｏＷＪ，ＷａｎｇＦ，ｅｔａｌ．Ａｓｅｌｆ⁃ａｓｓｅｍｂｌｅｄｃｏｕｍａｒｉｎ⁃ａｎｃｈｏｒｅｄｄｅｎｄｒｉｍｅｒｆｏｒｅｆｆｉｃｉｅｎｔｇｅｎｅｄｅｌｉｖｅｒｙａｎｄｌｉｇｈｔ⁃ｒｅｓｐｏｎｓｉｖｅｄｒｕｇｄｅｌｉｖｅｒｙ［Ｊ］．Ｂｉｏｍａｃｒｏｍｏｌｅｃｕｌｅｓ，２０１８，１９（６）：２１９４－２２０１．［１８］㊀ＣａｏＹ，ＨｕａｎｇＨＹ，ＣｈｅｎＬＱ，ｅｔａｌ．ＥｎｈａｎｃｅｄｌｙｓｏｓｏｍａｌｅｓｃａｐｅｏｆｐＨ⁃ｒｅｓｐｏｎｓｉｖｅｐｏｌｙｅｔｈｙｌｅｎｉｍｉｎｅ⁃ｂｅｔａｉｎｅｆｕｎｃｔｉｏｎａｌｉｚｅｄｃａｒｂｏｎｎａｎｏｔｕｂｅｆｏｒｔｈｅｃｏｄｅｌｉｖｅｒｙｏｆｓｕｒｖｉｖｉｎｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇＲＮＡａｎｄｄｏｘｏｒｕｂｉｃｉｎ［Ｊ］．ＡＣＳＡｐｐｌｉｅｄＭａｔｅｒｉａｌｓ＆Ｉｎｔｅｒｆａｃｅｓ，２０１９，１１（１０）：９７６３－９７７６．［１９］㊀ＸｕｅＬ，ＹａｎＹＦ，ＫｏｓＰ，ｅｔａｌ．ＰＥＩｆｌｕｏｒｉｎａｔｉｏｎｒｅｄｕｃｅｓｔｏｘｉｃｉｔｙａｎｄｐｒｏｍｏｔｅｓｌｉｖｅｒ⁃ｔａｒｇｅｔｅｄｓｉＲＮＡｄｅｌｉｖｅｒｙ［Ｊ］．ＤｒｕｇＤｅｌｉｖｅｒｙＡｎｄＴｒａｎｓｌａｔｉｏｎａｌＲｅｓｅａｒｃｈ，２０２１，１１（１）：２５５－２６０．［２０］㊀ＥｌＪｕｎｄｉＡ，ＭｏｒｉｌｌｅＭ，ＢｅｔｔａｃｈｅＮ，ｅｔａｌ．Ｄｅｇｒａｄａｂｌｅｄｏｕｂｌｅｈｙｄｒｏｐｈｉｌｉｃｂｌｏｃｋｃｏｐｏｌｙｍｅｒｓａｎｄｔｒｉｐａｒｔｉｔｅｐｏｌｙｉｏｎｉｃｃｏｍｐｌｅｘｍｉｃｅｌｌｅｓｔｈｅｒｅｏｆｆｏｒｓｍａｌｌｉｎｔｅｒｆｅｒｉｎｇｒｉｂｏｎｕｃｌｅｉｃａｃｉｄｓ（ｓｉＲＮＡ）ｄｅｌｉｖｅｒｙ［Ｊ］．ＪｏｕｒｎａｌｏｆＣｏｌｌｏｉｄＡｎｄＩｎｔｅｒｆａｃｅＳｃｉｅｎｃｅ，２０２０，５８０：４４９－４５９．［２１］㊀ＬｉＪ，ＬｉａｎｇＨ，ＬｉｕＪ，ｅｔａｌ．Ｐｏｌｙ（ａｍｉｄｏａｍｉｎｅ）（ＰＡＭＡＭ）ｄｅｎｄｒｉｍｅｒｍｅｄｉａｔｅｄｄｅｌｉｖｅｒｙｏｆｄｒｕｇａｎｄｐＤＮＡ／ｓｉＲＮＡｆｏｒｃａｎｃｅｒｔｈｅｒａｐｙ［Ｊ］．ＩｎｔｅｒｎａｔｉｏｎａｌＪｏｕｒｎａｌｏｆＰｈａｒｍａｃｅｕｔｉｃｓ，２０１８，５４６（１－２）：２１５－２２５．［２２］㊀ＭｏｕｓａｚａｄｅｈＨ，Ｐｉｌｅｈｖａｒ⁃ＳｏｌｔａｎａｈｍａｄｉＹ，ＤａｄａｓｈｐｏｕｒＭ，ｅｔａｌ．Ｃｙｃｌｏｄｅｘｔｒｉｎｂａｓｅｄｎａｔｕｒａｌｎａｎｏｓｔｒｕｃｔｕｒｅｄｃａｒｂｏｈｙｄｒａｔｅｐｏｌｙｍｅｒｓａｓｅｆｆｅｃｔｉｖｅｎｏｎ⁃ｖｉｒａｌｓｉＲＮＡｄｅｌｉｖｅｒｙｓｙｓｔｅｍｓｆｏｒｃａｎｃｅｒｇｅｎｅｔｈｅｒａｐｙ［Ｊ］．ＪｏｕｒｎａｌｏｆＣｏｎｔｒｏｌｌｅｄＲｅｌｅａｓｅ：ＯｆｆｉｃｉａｌＪｏｕｒｎａｌｏｆＴｈｅＣｏｎｔｒｏｌｌｅｄＲｅｌｅａｓｅＳｏｃｉｅｔｙ，２０２１，３３０：１０４６－１０７０．［２３］㊀ＣｈｏｉＢ，ＣｕｉＺＫ，ＫｉｍＳ，ｅｔａｌ．Ｇｌｕｔａｍｉｎｅ⁃ｃｈｉｔｏｓａｎｍｏｄｉｆｉｅｄｃａｌｃｉｕｍｐｈｏｓｐｈａｔｅｎａｎｏｐａｒｔｉｃｌｅｓｆｏｒｅｆｆｉｃｉｅｎｔｓｉＲＮＡｄｅｌｉｖｅｒｙａｎｄｏｓｔｅｏｇｅｎｉｃｄｉｆｆｅｒｅｎｔｉａｔｉｏｎ［Ｊ］．ＪｏｕｒｎａｌｏｆＭａｔｅｒｉａｌｓＣｈｅｍｉｓｔｒｙＢ，２０１５，３（３１）：６４４８－６４５５．［２４］㊀ＡｈｗａｚｉＲＰ，ＫｉａｎｉＭ，ＤｉｎａｒｖａｎｄＭ，ｅｔａｌ．ＩｍｍｏｂｉｌｉｚａｔｉｏｎｏｆＨＩＶ⁃１ＴＡＴｐｅｐｔｉｄｅｏｎｇｏｌｄｎａｎｏｐａｒｔｉｃｌｅｓ：ＡｆｅａｓｉｂｌｅａｐｐｒｏａｃｈｆｏｒｓｉＲＮＡｄｅｌｉｖｅｒｙ［Ｊ］．ＪｏｕｒｎａｌｏｆＣｅｌｌｕｌａｒＰｈｙｓｉｏｌｏｇｙ，２０２０，２３５（３）：２０４９－２０５９．［２５］㊀ＰｉｎｅｓｅＣ，ＬｉｎＪＱ，ＭｉｌｂｒｅｔａＵ，ｅｔａｌ．ＳｕｓｔａｉｎｅｄｄｅｌｉｖｅｒｙｏｆｓｉＲＮＡ／ｍｅｓｏｐｏｒｏｕｓｓｉｌｉｃａｎａｎｏｐａｒｔｉｃｌｅｃｏｍｐｌｅｘｅｓｆｒｏｍｎａｎｏｆｉｂｅｒｓｃａｆｆｏｌｄｓｆｏｒｌｏｎｇ⁃ｔｅｒｍｇｅｎｅｓｉｌｅｎｃｉｎｇ［Ｊ］．ＡｃｔａＢｉｏｍａｔｅｒｉａｌｉａ，２０１８，７６：１６４－１７７．［２６］㊀ＫｉｉｓｈｏｌｔｓＫ，ＫｕｒｒｉｋｏｆｆＫ，ＡｒｕｋｕｕｓｋＰ，ｅｔａｌ．Ｃｅｌｌ⁃ｐｅｎｅｔｒａｔｉｎｇｐｅｐｔｉｄｅａｎｄｓｉＲＮＡ⁃ｍｅｄｉａｔｅｄｔｈｅｒａｐｅｕｔｉｃｅｆｆｅｃｔｓｏｎｅｎｄｏｍｅｔｒｉｏｓｉｓａｎｄｃａｎｃｅｒｉｎｖｉｔｒｏｍｏｄｅｌｓ［Ｊ］．Ｐｈａｒｍａｃｅｕｔｉｃｓ，２０２１，１３（１０）：１６１８．［２７］㊀ＢｅｎＤＳ，Ｈｅｒｖé⁃ＡｕｂｅｒｔＫ，ＬａｊｏｉｅＬ，ｅｔａｌ．ｇＨ６２５ｃｅｌｌ⁃ｐｅｎｅｔｒａｔｉｎｇｐｅｐｔｉｄｅｐｒｏｍｏｔｅｓｔｈｅｅｎｄｏｓｏｍａｌｅｓｃａｐｅｏｆｎａｎｏｖｅｃｔｏｒｉｚｅｄｓｉＲＮＡｉｎａｔｒｉｐｌｅ⁃ｎｅｇａｔｉｖｅｂｒｅａｓｔｃａｎｃｅｒｃｅｌｌｌｉｎｅ［Ｊ］．Ｂｉｏｍａｃｒｏｍｏｌｅｃｕｌｅｓ，２０１９，２０（８）：３０７６－３０８６．［２８］㊀ＰｏｌａｎｃｏＪＣ，ＨａｎｄＧＲ，ＢｒｉｎｅｒＡ，ｅｔａｌ．Ｅｘｏｓｏｍｅｓｉｎｄｕｃｅｅｎｄｏｌｙｓｏｓｏｍａｌｐｅｒｍｅａｂｉｌｉｚａｔｉｏｎａｓａｇａｔｅｗａｙｂｙｗｈｉｃｈｅｘｏｓｏｍａｌｔａｕｓｅｅｄｓｅｓｃａｐｅｉｎｔｏｔｈｅｃｙｔｏｓｏｌ［Ｊ］．ＡｃｔａＮｅｕｒｏｐａｔｈｏｌｏｇｉｃａ，２０２１，１４１（２）：２３５－２５６．［２９］㊀ＸｕＬＺ，ＦａｒｕｑｕＦＮ，ＬｉｍＹＭ，ｅｔａｌ．Ｅｘｏｓｏｍｅ⁃ｍｅｄｉａｔｅｄＲＮＡｉｏｆＰＡＫ４ｐｒｏｌｏｎｇｓｓｕｒｖｉｖａｌｏｆｐａｎｃｒｅａｔｉｃｃａｎｃｅｒｍｏｕｓｅｍｏｄｅｌａｆｔｅｒｌｏｃｏ⁃ｒｅｇｉｏｎａｌｔｒｅａｔｍｅｎｔ［Ｊ］．Ｂｉｏｍａｔｅｒｉａｌｓ，２０２１，２６４：１２０３６９．［３０］㊀ＫｈｅｌｇｈａｔｉＮ，ＳｏｌｅｉｍａｎｐｏｕｒＭｏｋｈｔａｒｖａｎｄＪ，ＭｉｒＭ，ｅｔａｌ．Ｔｈｅｉｍｐｏｒｔａｎｃｅｏｆｃｏ⁃ｄｅｌｉｖｅｒｙｏｆｎａｎｏｐａｒｔｉｃｌｅ⁃ｓｉＲＮＡａｎｄａｎｔｉｃａｎｃｅｒａｇｅｎｔｓｉｎｃａｎｃｅｒｔｈｅｒａｐｙ［Ｊ］．ＣｈｅｍｉｃａｌＢｉｏｌｏｇｙ＆ＤｒｕｇＤｅｓｉｇｎ，２０２１，９７（４）：９９７－１０１５．［３１］㊀ＡｎｓａｒＳＭ，ＭｕｄａｌｉｇｅＴ．Ｃｈａｒａｃｔｅｒｉｚａｔｉｏｎｏｆｄｏｘｏｒｕｂｉｃｉｎｌｉｐｏｓｏｍａｌｆｏｒｍｕｌａｔｉｏｎｓｆｏｒｓｉｚｅ⁃ｂａｓｅｄｄｉｓｔｒｉｂｕｔｉｏｎｏｆｄｒｕｇａｎｄｅｘｃｉｐｉｅｎｔｓｕｓｉｎｇａｓｙｍｍｅｔｒｉｃ⁃ｆｌｏｗｆｉｅｌｄ⁃ｆｌｏｗｆｒａｃｔｉｏｎａｔｉｏｎ（ＡＦ４）ａｎｄｌｉｑｕｉｄｃｈｒｏｍａｔｏｇｒａｐｈｙ⁃ｍａｓｓｓｐｅｃｔｒｏｍｅｔｒｙ（ＬＣ⁃ＭＳ）［Ｊ］．ＩｎｔｅｒｎａｔｉｏｎａｌＪｏｕｒｎａｌｏｆＰｈａｒｍａｃｅｕｔｉｃｓ，２０２０，５７４：１１８９０６．（２０２１－１１－１６收稿，２０２２－０７－２１修回）㊃５４５㊃第５期㊀㊀㊀㊀㊀㊀王飞，等：ｓｉＲＮＡ非病毒载体递送用于肿瘤治疗的研究进展。

口服药还有吗英语作文

口服药还有吗英语作文Title: The Future of Oral Medications。

In recent years, the world has witnessed remarkable advancements in medical science, particularly in the realm of drug delivery methods. Among these, oral medications have long been a cornerstone of treatment regimens for various ailments. However, with the advent of new technologies and innovative approaches, the landscape of drug administration is undergoing significant transformation. This essay delves into the evolving role of oral medications in the context of modern medicine.Firstly, it is imperative to acknowledge the enduring relevance of oral medications. Their convenience, non-invasiveness, and ease of administration make them highly desirable for patients and healthcare providers alike. From pain relievers to chronic disease management, oral drugs have proven their efficacy across a spectrum of medical conditions. Moreover, the oral route offers flexibility indosing regimens and facilitates self-administration, empowering patients to take control of their health.Nevertheless, the traditional oral drug delivery system is not without its limitations. Variability in absorption rates, degradation in the gastrointestinal tract, and the first-pass effect pose challenges to achieving optimal therapeutic outcomes. To address these issues, researchers are exploring innovative solutions to enhance the efficacy and reliability of oral medications.One promising avenue is the development of advanced drug delivery technologies. Nanotechnology, for instance, enables the formulation of drug particles at the nanoscale, enhancing their bioavailability and targeting specific tissues or cells. Nanocarriers such as liposomes and polymeric nanoparticles protect drugs from degradation and facilitate controlled release, thereby improving therapeutic efficacy. Furthermore, the integration of smart materials and stimuli-responsive systems enables precise control over drug release kinetics, ensuring sustained and targeted delivery.Moreover, the emergence of biopharmaceuticals,including peptides, proteins, and nucleic acids, presents both opportunities and challenges for oral drug delivery. These macromolecular drugs offer immense therapeutic potential but are inherently susceptible to degradation and poor absorption in the gastrointestinal tract. Nonetheless, innovative formulation strategies, such as encapsulation in nanoparticles or mucoadhesive systems, hold promise for overcoming these barriers and unlocking the full therapeutic benefits of biopharmaceuticals via oral administration.Furthermore, advancements in personalized medicine and pharmacogenomics are reshaping the landscape of drug development and prescription. Tailoring treatment regimens based on individual genetic profiles and physiological characteristics allows for optimized dosing, reduced adverse effects, and improved patient outcomes. In the realm of oral medications, personalized approaches may involve the development of patient-specific formulations or the use of drug delivery systems tailored to individualpharmacokinetic parameters.In addition to technological innovations, the integration of digital health solutions is revolutionizing medication management and adherence. Smart pill technologies, equipped with sensors and connectivity features, enable real-time monitoring of patient compliance and therapeutic response. These digital platforms not only facilitate remote patient monitoring but also empower healthcare providers to intervene promptly in case of non-adherence or adverse events, thereby improving treatment outcomes and reducing healthcare costs.However, despite these advancements, challenges persist in the widespread adoption of oral medications,particularly in resource-limited settings and underserved populations. Issues such as medication affordability, accessibility, and health literacy must be addressed to ensure equitable access to cutting-edge therapies. Furthermore, regulatory frameworks need to evolve to accommodate the complexities of novel drug delivery systems and biopharmaceuticals, balancing innovation with safetyand efficacy considerations.In conclusion, while oral medications remain a cornerstone of modern healthcare, ongoing research and innovation are reshaping their role and efficacy. From advanced drug delivery technologies to personalized medicine and digital health solutions, the future holds immense promise for enhancing the therapeutic potential of oral medications. By overcoming existing challenges and embracing emerging opportunities, we can ensure that oral drugs continue to play a pivotal role in improving patient outcomes and advancing medical science.。

英语作文-快递服务行业的服务质量评估与改进机制

英语作文-快递服务行业的服务质量评估与改进机制The assessment and improvement mechanism of service quality in the express delivery industry is crucial for enhancing customer satisfaction and operational efficiency. In recent years, the rapid growth of e-commerce has propelled the demand for reliable and efficient delivery services. As a result, evaluating and continuously improving service quality has become a focal point for companies within this sector.Firstly, a pivotal aspect of evaluating service quality in the express delivery industry is reliability. Customers expect their parcels to be delivered on time and in good condition. Therefore, tracking the percentage of deliveries made according to the promised timeline provides a measurable indicator of reliability. Companies often use key performance indicators (KPIs) such as on-time delivery rate and delivery accuracy to assess their performance in this area.Moreover, the responsiveness of delivery services is another critical dimension of service quality. It involves the speed and effectiveness with which customer inquiries and issues are addressed. A prompt response to customer queries regarding shipment status or complaints about damaged goods reflects the company's commitment to service excellence. Utilizing customer feedback mechanisms, such as surveys or feedback forms, enables companies to gauge customer satisfaction levels and identify areas for improvement.Additionally, the competence of delivery personnel significantly influences service quality. Couriers who are well-trained not only in handling parcels securely but also in providing courteous and professional customer interactions contribute positively to overall service experience. Regular training programs and performance evaluations help maintain high standards of competence among delivery staff, ensuring consistent service quality.Furthermore, the tangibles associated with delivery services, such as packaging quality and technological interfaces, also impact customer perceptions. Companies that invest in robust packaging materials to protect goods during transit demonstrate a commitment to delivering parcels in optimal condition. Similarly, user-friendly mobile apps or websites that provide real-time tracking and convenient scheduling options enhance the overall customer experience.The reliability, responsiveness, competence of personnel, and tangibles collectively contribute to the perceived service quality in the express delivery industry. Continuous improvement efforts are essential to meet evolving customer expectations and stay competitive in the market. Regular audits and performance reviews help identify operational bottlenecks or service gaps that need attention.In conclusion, the express delivery industry relies heavily on maintaining high service quality standards to foster customer loyalty and sustain business growth. By focusing on aspects such as reliability, responsiveness, personnel competence, and tangible service features, companies can effectively assess their performance and implement targeted improvements. Embracing a culture of continuous improvement ensures that service quality remains a cornerstone of competitive advantage in this dynamic industry landscape.。

电商未来规划英语作文

电商未来规划英语作文The rapid development of ecommerce has revolutionized the way we shop and conduct business. As we look to the future its essential to plan strategically to stay competitive and innovative. Heres an essay on the future planning of ecommerceTitle The Future of Ecommerce Strategic Planning for SuccessIntroductionEcommerce has transformed the global marketplace offering consumers unprecedented convenience and businesses new avenues for growth. As we peer into the future its clear that ecommerce will continue to evolve presenting both opportunities and challenges. This essay will explore the key areas of focus for future ecommerce planning including technological advancements customer experience sustainability and regulatory compliance.Body1. Embracing Technological InnovationsThe integration of artificial intelligence AI for personalized shopping experiences.Utilizing big data for better inventory management and market analysis.Implementing augmented reality AR and virtual reality VR for immersive shopping experiences.2. Enhancing Customer ExperiencePrioritizing userfriendly interfaces and seamless navigation.Offering personalized recommendations and targeted marketing.Ensuring fast and reliable delivery services to meet customer expectations.3. Focusing on SustainabilityAdopting ecofriendly packaging and shipping methods.Promoting sustainable sourcing and production practices.Encouraging customers to make environmentally conscious choices.4. Adapting to Regulatory ChangesStaying informed about evolving ecommerce regulations in different jurisdictions.Ensuring data privacy and security to protect customer information.Complying with tax laws and international trade agreements.5. Expanding Global ReachDeveloping strategies for entering new markets and understanding cultural nuances. Overcoming language barriers through multilingual platforms and customer support. Adapting payment and logistics solutions to cater to diverse customer needs.6. Fostering a Strong Brand IdentityBuilding trust through transparent business practices and ethical standards.Differentiating from competitors by highlighting unique selling propositions.Engaging with customers through social media and content marketing.ConclusionThe future of ecommerce is promising yet challenging. By focusing on technological innovation enhancing customer experience embracing sustainability adapting to regulatory changes expanding global reach and fostering a strong brand identity businesses can position themselves for success in the dynamic ecommerce landscape. With strategic planning and a commitment to excellence ecommerce platforms can continue to thrive and shape the future of global trade.This essay provides a comprehensive overview of the key considerations for ecommerce businesses as they plan for the future. By addressing these areas companies can ensure they remain competitive and relevant in an everevolving digital marketplace.。