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Fe3O4@SiO2磁性纳米粒子的制备及表征

Fe3O4@SiO2磁性纳米粒子的制备及表征

Fe3O4@SiO2磁性纳米粒子的制备及表征杜雪岩;马芬;李芳;徐凯【摘要】用多元醇还原法制备出平均粒径为6.0 nm的Fe3O4磁性纳米粒子,并用盐酸溶液(1 mol/L)对其进行酸化处理,然后利用反相微乳液法,在Op-10/正丁醇/环己烷/浓氨水反相微乳体系中制备出Fe3O4@SiO2磁性纳米复合粒子.利用X射线衍射(XRD)仪,透射电子显微镜(TEM),傅立叶-红外光谱仪(FT-IR)和振动样品磁强计(VSM)对复合粒子进行表征.结果表明:SiO2成功包覆在Fe3O4磁性纳米粒子表面,制得的复合粒子平均粒径为25.0 nm,呈球形且分散均匀,包覆后饱和磁化强度有所下降,但矫顽力仍趋近于零,显示超顺磁性.%The Fe3O4 magnetite nano-particles with average particle size of about 6. 0 nm were prepared with polyol reduction method. Then the magnetite nanoparticles were acidized with hydrochloric acid solution(1 mol/L). Finally, Fe3O4@SiO2 composite nanoparticles were synthesized in OP-10/n-butanol/cyclohexane/ammonia reverse micro-emulsion system. The composite nanoparticles were characterized with X-ray powder diffraction (XRD), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and vibrating sample magnetometer (VSM). The result showed that the surface of Fe3O4 nanoparticles was successfully coated by the silica. The**********************************************,weresphericalin shape and dispersed more uniformlly. As the coating had performed, the specific saturation magnetization decreased to some extent, but the coercivity was still close to zero, manifesting their superparamagnetic properties.【期刊名称】《兰州理工大学学报》【年(卷),期】2011(037)002【总页数】4页(P22-25)【关键词】反相微乳液;Fe3O4纳米粒子;Fe3O4@SiO2复合粒子【作者】杜雪岩;马芬;李芳;徐凯【作者单位】兰州理工大学,甘肃省有色金属新材料重点实验室,甘肃,兰州,730050;兰州理工大学,有色金属合金及加工教育部重点实验室,甘肃兰州,730050;兰州理工大学,甘肃省有色金属新材料重点实验室,甘肃,兰州,730050;兰州理工大学,有色金属合金及加工教育部重点实验室,甘肃兰州,730050;兰州理工大学,甘肃省有色金属新材料重点实验室,甘肃,兰州,730050;兰州理工大学,有色金属合金及加工教育部重点实验室,甘肃兰州,730050;兰州理工大学,甘肃省有色金属新材料重点实验室,甘肃,兰州,730050;兰州理工大学,有色金属合金及加工教育部重点实验室,甘肃兰州,730050【正文语种】中文【中图分类】TB33;TM271近年来，Fe3 O4磁性纳米粒子由于同时具备磁性颗粒和纳米颗粒的双重优势，已经广泛应用于靶向药物载体、细胞分离、核磁共振、免疫分析、核酸杂交等生物医学领域［1－4］.同时，这种超顺磁性材料在催化领域也具有很好的应用前景，可以作为液相小尺寸催化剂的催化载体［5－7］，改善催化剂分离难的状况.但是Fe3 O4磁性纳米粒子易氧化，比表面积较高，具有强烈的聚集倾向［8］，难以直接应用.采用无定型SiO2对Fe3 O4磁性纳米粒子进行表面包覆［9－10］，SiO2包覆层增加了其化学稳定性，同时 SiO2的无毒性和表面羟基的存在提高了其生物相容性［11－12］，拓宽了 Fe3 O4 磁性纳米粒子在生物、催化等领域的应用.本文参照JIN Xie等人［13］的多元醇还原法，用1-2十二烷二醇代替1-2十六烷二醇制备出Fe3 O4磁性纳米粒子，该法制备的磁性粒子纯度高，粒度细，单分散，稳定性好.由于加入了表面活性剂油酸，其极性羧基端直接吸附于Fe3 O4颗粒表面，非极性的碳链端伸入水相中，可以阻止Fe3 O4微粒的聚集长大，但由于表面的疏水性，在水中易沉降，难分散，制得的Fe3 O4纳米粒子表现亲油性，WANG等人［14］运用油酸与α－环糊精的主客体相互作用，将粒子由油溶性转化为水溶性；SUN等人［15］用11－胺基十一酸四甲基铵置换Fe3 O4表面的油酸，油胺实现了纳米粒子的水溶性.本文在包覆前用盐酸溶液（1 mol／L）处理Fe3 O4纳米粒子，然后采用反相微乳液法，在OP-10／正丁醇／环己烷／浓氨水反相微乳体系中以Fe3 O4为种子，用氨水催化正硅酸乙酯水解［16－17］，合成了粒径均匀的 Fe3 O4＠SiO2磁性纳米粒子，并对其进行了结构和磁性能的表征.1 实验1.1 试剂与仪器所用主要试验试剂有：乙酰丙酮铁（新泽西美国生产，分析纯）、1-2十二烷二醇（东京化成工业株式会社生产，分析纯）、无水乙醇（天津市化学试剂二厂生产，分析纯）、油酸（天津市恒兴化学试剂制造有限公司生产，分析纯）、油胺（东京化成工业株式会社生产，分析纯）、二苄醚（Alfa Aesar A Johnson Matthey Company生产，分析纯）、乳化剂 OP-10（天津市光复精细化工研究所生产，分析纯）、正丁醇（天津市科密欧化学试剂有限公司生产，分析纯）、氨水（白银化学试剂厂生产，分析纯）、环己烷（天津市巴斯夫化工有限公司生产，分析纯）、TEOS（上海试剂一厂生产，分析纯）.实验仪器有：FA2104N型分析天平（上海精密科学仪器有限公司生产），78-1型磁力加热搅拌器（江苏省金坛市荣华仪器制造有限公司生产），金怡牌KDM型调温电热套（江苏省金坛市医疗仪器厂生产），DZF-6050型真空干燥箱（上海精密实验设备有限公司生产）.1.2 Fe3 O4纳米粒子的制备将0.703 5 g的Fe（acac）3，2.079 8 g的1-2十二烷二醇置于250 m L四口圆底烧瓶中，再依次加入40.0 m L无水乙醇，2.0 m L油酸，2.0 m L油胺和20.0 m L二苄醚，在氩气保护下磁力搅拌至溶解.然后把混合溶液加热到200℃并保温2 h，继续加热到回流温度，保温1 h.关闭加热源在室温下冷却至黑褐色产物，然后用无水乙醇清洗产物数次得到亲油性的Fe3 O4纳米粒子.1.3 Fe3 O4纳米粒子的酸洗处理称取0.023 2 g的Fe3 O4纳米粒子，加入到5.0 m L的 HCl（1 mol／L）溶液中，超声振荡一定时间后，用离心机将粒子分离出来，分散在去离子水中.通过酸洗处理可以改变Fe3 O4纳米粒子表面所带电荷的性质，使其由亲油性转化为亲水性. 1.4 Fe3 O4＠SiO2纳米粒子的制备以OP-10、正丁醇、环己烷和浓氨水分别作为表面活性剂、助表面活性剂，油相和水相，按一定的比例混合配成微乳液体，剧烈搅拌，再依次加入酸洗处理过的Fe3 O4胶体溶液和TEOS.反应完成后使用体积比为75%的丙酮水溶液破乳，静置分层后，去除上清液，对下层沉淀物用乙醇清洗数次，最后得到Fe3 O4＠SiO2磁性纳米复合粒子.2 结果与讨论2.1 XRD分析图1为Fe3 O4纳米粒子和Fe3 O4＠SiO2复合纳米粒子的XRD图谱，将图1中a线与Fe3 O4的粉末衍射卡（JCPDS，75-1610）对比，出现了明显的（220）、（311）、（400）、（422）、（511）、（440）等特征衍射峰，可知磁性纳米粒子物相为反尖晶石结构的的Fe3 O4，峰型尖锐，说明结晶完整.而从图1中b线上可发现在2θ为25°附近有一较宽的弥散峰，说明有非晶态的物质SiO2的存在，其余衍射峰则和Fe3 O4的特征峰对应，表明包覆后Fe3 O4纳米粒子的晶体结构没有改变，但峰强有所减弱，这是因为表面包覆了SiO2造成的. 图1 Fe3 O4和Fe3 O4＠SiO2纳米粒子的XRD图谱Fig.1 XRD patterns of Fe3 O4 and Fe3 O4＠SiO2 nanoparticles2.2 FT-IR 分析图2是Fe3 O4纳米粒子和Fe3 O4＠SiO2复合纳米粒子的红外光谱图，图2中a 线上577.3 cm－1处对应 Fe3 O4 的 Fe—O 特征峰，3 422.1 cm－1和1 629.7 cm－1处对应其表面羟基—OH的伸缩振动峰和弯曲振动峰.而从图2中b线上看到，Fe3 O4表面包覆了SiO2后Fe—O特征峰从577.3 cm－1处移到了586.8 cm－1处，发生了“红移”.另外，795.4 cm－1处和468.3 cm－1处分别对应Si—O的对称伸缩振动和弯曲振动，而在1 097.2 cm－1处出现的新的吸收谱带是Si—O的反对称伸缩振动谱带.图2 Fe3 O4和Fe3 O4＠SiO2纳米粒子的红外光谱分析Fig.2 FT-IR spectra of Fe3 O4 and Fe3 O4＠SiO2 nanoparticles2.3 TEM 分析图3a是Fe3 O4纳米粒子的TEM图，由图可见，Fe3 O4粒子呈球状，平均粒径在6.0 nm左右，分散性较好.图3b～d是复合粒子的图片，由图可见，所有的Fe3 O4粒子都已经被SiO2包覆，深色部分为Fe3 O4纳米粒子，包裹在外层的灰色物质为SiO2壳层.图3b，c出现了SiO2包覆多个Fe3 O4粒子的情况，这是因为当TEOS的含量过高时，溶液离子强度增大且粒子表面电位降低［18］，使得Fe3 O4种子在包覆之前出现了失稳和团聚现象，从而出现SiO2包覆多个Fe3 O4粒子的情况.随着TEOS量的减小，从图3d可见复合粒子分散性有所提高，大小更加均匀.当摩尔比nFe3O4∶nTEOS＝1∶10时制得的复合粒子平均粒径在25.0 nm左右，膜厚约为9.0 nm.图3 Fe3 O4和Fe3 O4＠SiO2纳米粒子的TEM图谱Fig.3 TEM images of Fe3 O4 and Fe3 O4＠SiO2 nanoparticles2.4 VSM 分析图4为Fe3 O4纳米粒子和摩尔比nFe3O4∶nTEOS＝1∶10时制得的Fe3 O4＠SiO2复合纳米粒子的磁滞回线.由图4中a线看到，Fe3 O4磁性纳米粒子饱和磁化强度约为67 A·m2／kg，矫顽力趋近于零，具有良好的超顺磁性.从图4中b线看到SiO2包裹后饱和磁化强度约为15 A·m2／kg，矫顽力基本保持不变仍具有良好的超顺磁性，Ms下降是由于包覆了SiO2后，产物中的Fe3 O4的相对含量降低，其次，由于SiO2层的包覆使粒子的粒径发生了变化，从而导致磁性的变化. 图4 Fe3 O4和Fe3 O4＠SiO2复合纳米粒子的磁滞回线Fig.4 Hysteresis loops of Fe3 O4 and Fe3 O4＠SiO2 nanoparticles3 结论1）采用多元醇还原法制备出油溶性的Fe3 O4纳米粒子，粒子近似球形，分散性较好，粒径分布均匀，大小约为6.0 nm.矫顽力趋近于零，显示超顺磁性.2）对制得的Fe3 O4纳米粒子进行酸化处理，使其转变为亲水性粒子，然后采用OP-10／正丁醇／环己烷／浓氨水反相微乳体系成功制备出核壳结构的Fe3 O4＠SiO2复合纳米粒子，粒子形貌光滑，呈球形且分散均匀，大小约为25.0 nm.矫顽力不变趋近于零，仍然显示超顺磁性.致谢：本文得到兰州理工大学博士基金项目（SB01200602）的资助，在此表示感谢.参考文献：［1］ MORNET S，VASSEUR S，GRASSET F，etal.Magnetic nanoparticle design for medical dia-gnosis and therapy［J］.J Mater Chem，2004，14（14）：2161-2175.［2］ PANKHURST Q A，CONNOLLY J，JONES S K，etal.Applications of magnetic nanoparticles in biomedicine［J］.Phys D：Appl Phys，2003，36（13）：167-181.［3］ SUN CONROY，LEE JERRY S H，ZHANG Miqin.Magnetic nanoparticles in MR imaging and drug delivery［J］.Adv Drug Delivery Rev，2008，60（11）：1252-1265.［4］ AJAY KUMAR GUPTA，MONA GUPTA.Synthesis and surface engineering of iron oxide nanoparticles for biomedical applications［J］.Biomaterials，2005，26（18）：3995-4021.［5］ STEVENS P D，LI G，FAN J，etal.Recycling of homogeneous Pd catalysts using superparamagnetic nanoparticles as novel soluble supports for Suzuki，Heck，and Sonogashira cross-coupling reactions［J］.Chem Commun，2005，35（2）：4435-4437.［6］ STEVENS P D，FAN J，GARDIMALLA H M R，etal.Super paramagnetic nanoparticle-supported catalysis of suzuki cross coupling reactions［J］.Org Lett，2005，7（11）：2085-2088.［7］ WANG Z F，XIAO P F，SHEN B，etal.Synthesis of palladium coated magnetic nanoparticle and its application in Heck reaction［J］.Colloids and Surfaces A，2006，276（1／2／3）：116-121.［8］ LU A H，SALABAS E L，SCH¨UTH F.Magnetic nanoparticles：synthesis，protection，functionalization，and application［J］.Angew Chem Int Ed，2007，46（8）：1222-1244.［9］ CHEN F H，GAO Q，NI J Z.The grafting and release behavior of doxorubincin from Fe3 O4＠SiO2 core-shell structure nanoparticles via an acid cleaving amide bond：the potential for magnetic targeting drug delivery ［J］.Nanotechnology，2008，19（16）：165103.1-165301.9. ［10］ SANTRA S，TAPEC R，THEODOROPOULOU N，etal.Synthesis and characterization of silica-coated iron oxide nanoparticles in microemulsion：the effect of nonionic surfactants［J］.Langmuir，2001，17（10）：2900-2906.［11］ LU C W，HUNG Y，HSIAO J K，etal.Bifunctional magnetic silica nanoparticles for highly efficient human stem cell labeling［J］.Nano Lett，2007，7（1）：149-154.［12］ YOON T J，KIM J S，KIM B G，etal.Multifunctional nanoparticles possessing a“magnetic motor effect”for drug or gene delivery［J］.Angew Chem Int Ed，2005，44（7）：1068-1071.［13］ JIN Xie，SHENG Peng，NATHAN BROWER，etal.One-pot synthesis of monodisperse iron oxide nanoparticles for potential biomedical applications［J］.Pure Appl Chem，2006，78（5）：1003-1014.［14］ WANG Y，YANG H，TENG X，etal.“Pulling”nanoparticles into water：phase transfer of oleic acid stabilized monodisperse nanoparticles into aqueous solutions ofα-cyclodextrin ［J］.Nano lett，2003，3（11）：1555-1559.［15］ SUN S H，ZENG H，RIBINSON D B，etal.Mono-disperse MFe2 O4（M＝Fe，Co，Mn）nanoparticles［J］.J Am Chen Soc，2004，126（1）：273-279.［16］刘冰，王德平，姚爱华，等.反相微乳液法制备核壳Fe3 O4／SiO2复合纳米粒子［J］.硅酸盐学报，2008，36（4）：569-574.［17］杜雪岩，郭海霞，李翠霞，等.SiO2包覆FePt磁性纳米颗粒的制备和其磁性能［J］.兰州理工大学学报，2010，36（3）：22-24.［18］ NAGAO D，SATOH T，KONNO M.A generalized model for describing particle formation in the synthesis of monodisperse oxide particles based on the hydrolysis and condensation of tetraethyl orthosilicate［J］.Journal of Colloid and Interface Science，2000，232（1）：102-110.。

10四氧化三铁磁性纳米材料具有辣根过氧化物酶活性

10四氧化三铁磁性纳米材料具有辣根过氧化物酶活性

四氧化三铁磁性纳米材料具有辣根过氧化物酶活性高利增1 庄洁1 聂棱2 张锦彬1 张宇3 顾宁3 王太宏2杨东玲1 冯静1 Sarah Perrett1 阎锡蕴1,*(1中国科学院生物物理研究所 生物大分子国家重点实验室 北京 100101；中国科学院物理研究所 北京 100190； 3东南大学 生物电子学国家重点实验室 南京 210096)摘要: 磁性纳米材料一直被认为是一种惰性材料，被广泛的应用于生物分离、核磁成像等多个领域。

我们首次发现Fe3O4磁性纳米材料具有辣根过氧化物酶的活性，能够催化过氧化氢发生氧化还原反应。

通过对Fe3O4磁性纳米材料与辣根过氧化物酶的酶动力学特性进行比较，发现Fe3O4磁性纳米材料具有和辣根过氧化物酶类似的催化活性。

Intrinsic Peroxidase-like Activity of Ferromagnetic NanoparticlesGAO Lizeng 1,2,5, ZHUANG Jie1,2,5 , NIE Leng3,5, ZHANG Jinbin 1,2,5,ZHANG Yu 4, GU Ning4, WANG Taihong3, FENG Jing 1,2,YANG Dongling 1,2, Sarah Perrett1,* and YAN Xiyun1,2*(1National Laboratory of Biomacromolecules and 2Chinese Academy of Sciences – University of Tokyo Joint Laboratory of Structural Virology and Immunology, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Beijing 100101, China. 3Institute of Physics, Chinese Academy of Sciences, Beijing 10080, China. 4State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China. 5Graduate School of the Chinese Academy of Sciences, Beijing, 100049, China.)Abstract: Nanoparticles have been used increasingly in medical and technological applications. Nanoparticles containing magnetic materials, such as magnetite (Fe3O4), are particularly powerful in imaging or separation techniques. These nanoparticles are generally considered to be biologically and chemically inert. Typically, the nanoparticle surface is functionalised by conjugation with antibodies or enzymes, or coating with metal catalysts. Here, we report a nanomaterial that can be used directly as an enzyme mimetic.We found that magnetite nanoparticles possess intrinsic peroxidase activity, which is pH, temperature, particle-size and H2O2 concentration dependent. The activity shows typicalMichaelis-Menten kinetics and double-reciprocal plots indicate a ping-pong mechanism.We found that magnetite nanoparticles could be coated with dextran to improve作者简介：阎锡蕴，女，医学博士，中国科学院生物物理研究所研究员，博士生导师；主要研究肿瘤新型靶分子和抗体的作用机制，结合纳米材料和技术研制新型肿瘤免疫诊断和靶向治疗的方法。

细胞核磁共振技术的应用前景

细胞核磁共振技术的应用前景

细胞核磁共振技术的应用前景细胞核磁共振技术（Cellular Magnetic Resonance Imaging，CMRI）是一种新兴的影像学技术，可以在分子、细胞和组织水平上观察生物体的内部结构、功能和代谢，并为医学和生物科学研究提供了极为有价值的信息。

随着科技不断进步，CMRI技术在医学和生命科学领域的应用越来越广泛。

CMRI技术不同于传统MR技术，它可以直接在活细胞水平上获取瞬时的、空间分辨率高、对酶反应、信号通路调控、代谢路劲等细胞生理活动的信息。

CMRI技术首先在肿瘤的诊断中有了应用，其中最具有代表性的研究是针对肝细胞癌（hepatocellular carcinoma，HCC）的诊断。

该技术可以用皮下注射的方式，将铁金属粒子（iron oxide nanoparticles，IONPs）注入HCC细胞，通过磁共振成像（Magnetic Resonance Imaging，MRI）对导入的IONPs进行调制，从而实现对癌细胞的成像和定位。

研究揭示了CMRI在癌症治疗中的作用。

CMRI技术可以通过对肿瘤细胞内部分子代谢水平的监测，更准确地评估癌细胞对药物的敏感性和耐药性。

此外，CMRI技术也能够跟踪肿瘤细胞的迁移，为肿瘤治疗提供进一步的指导。

CMRI技术在神经科学领域的应用也日益受到关注。

研究表明，CMRI可以在小鼠和猴子的大脑中实现活细胞水平的神经元成像，探索生物体内神经元的连接方式和神经网络的结构和功能。

特别是，CMRI技术在揭示神经网络中单个神经元的功能机制、神经回路中神经元间的信号传递机制等方面具有重要的应用前景，会对神经科学研究的发展产生深远的影响。

除了在癌症和神经科学领域，CMRI技术还在心脏、肌肉、骨骼和器官等领域的研究中得到了应用。

例如在心脏领域中，CMRI技术可以对基质、心肌细胞和心肌细胞内Ca2+浓度等进行高分辨率的成像，进而深入研究心脏的生理和病理机制，促进心脏疾病的研究和治疗。

PETMR双模态分子影像探针的研究进展

PETMR双模态分子影像探针的研究进展

P E T /M R 双模态分子影像探针的研究进展王㊀敏,张㊀立,李海燕,丁㊀颖,柳㊀宇,曹㊀卫(华中科技大学同济医学院附属协和医院核医学科㊁分子影像湖北省重点实验室,湖北武汉４３００２２)D O I :１０．１１７４８/b j m y ．i s s n ．１００６－１７０３．２０２１．０１．０３６收稿日期:２０２０Ｇ０９Ｇ０３;修回日期:２０２０Ｇ１１Ｇ１７基金项目:科技部国家重点研发计划(编号:２０１７Y F ０１３３０２)通讯作者:曹卫(１９７０ ),博士,教授,博士生导师,从事分子影像及核素治疗.E Ｇm a i l :c a o w e i ＠h u s t ．e d u ．c n摘要:当今分子影像技术在疾病的个体化诊疗中起着至关重要的作用.由于每种显像技术都有其自身的局限性,多模态成像已成为当前分子影像领域发展的主流.基于一体化P E T/M R 成像设备的广泛应用,P E T /M R 双模态探针由于综合了高分辨率和高灵敏度的优点引起人们的极大关注.本文对P E T /M R 双模态分子探针的发展现状和应用前景进行综述.关键词:分子探针;㊀双模态;㊀P E T 成像;㊀磁共振成像中图分类号:R ８１７．８㊀㊀文献标识码:A T h eR e s e a r c hP r o g r e s s o fP E T /M RB i m o d a l i t y M o l e c u l a r I m a g i n g Pr o b e s WA N G M i n ,Z H A N G L i ,L IH a i y a n ,D I N G Y i n g,L I U Y u ,C A O W e i (D e p a r t m e n t o fN u c l e a rM e d i c i n e ,U n i o nH o s p i t a l ,T o n g j iM e d i c a l C o l l e g e ,H u a z h o n g U n i v e r s i t y o f S c i e n c e a n dT e c h n o l o g y;H u b e i P r o v i n c eK e y L a b o r a t o r y o fM o l e c u l a r I m a g i n g,W u h a n ４３００２２,C h i n a )A b s t r a c t :N o w a d a y sm o l e c u l a r i m a g i n gp l a y sav i t a l r o l e i na c h i e v i n g as u c c e s s f u l t a r g e t e da n d p e r s o n a l i z e d t r e a t m e n t ．M o r e i n t e r e s t s i n t h ed e v e l o p m e n t o fm o l e c u l a r i m a g i n g h a v eb e e n s h i f t e d t o w a r dm u l t i m o d a l i t yi m a g i n g ,b e c a u s eo f t h e f a c t t h a tn os i n g l e i m a g i n g m o d a l i t yp o s s e s s e sa l l i d e a l t r a i t s ．B a s e do nt h e T O F ＧP E T /MR ,t h eP E T /MR b i m o d a l p r o b eh a s r e c e i v e d m o r ea t t e n t i o n sd u et oi t s c h a r a c t e r i s t i c sw i t ht h e c o m b i n a t i o no f h i g h a n a t o m i c r e s o l u t i o n a n dh i g h s e n s i t i v i t y ．H e r e i n ,t h i s a r t i c l e r e po r t s t h e l a t e s t p r o g r e s s i n t h e f i e l do fP E T /MRb i m o d a lm o l e c u l a r p r o b e s ,a n d s u mm a r i z e s t h e p r o s p e c t s ．K e y w o r d s :M o l e c u l a r p r o b e s ;㊀B i m o d a l i t y i m a g i n g;㊀P E T ;㊀MR I ㊀㊀分子影像(m o l e c u l a r i m a g i n g )是应用影像学方法,在组织水平㊁细胞水平甚至分子水平对特定的分子进行活体成像以显示其生物学行为,并对之进行定性㊁定量研究[１].近十年来,分子成像技术不断发展,光学成像(o p t i c a l i m a g i n g,O I )㊁电子计算机断层扫描(c o m p u t e dt o m o g r a p h y ,C T )㊁磁共振成像(m a gn e t i c r e s o n a n c e i m a g i n g ,M R I )㊁正电子发射型计算机断层扫描(p o s i t r o ne m i s s i o n t o m o g r a p h y ,P E T )和单光子发射型计算机断层扫描(s i n gl e p h o t o ne m i s s i o n c o m p u t e d t o m o g r a p h y,S P E C T )等在疾病监测㊁临床诊断与治疗等方面均展现出巨大的应用潜力.但是每个单一的分子成像技术(模态)都有其自身的缺点,如在分辨率㊁灵敏度㊁及特异性等方面存在不足.双模态分子探针则通过组合两种成像技术的优点,可获得一些全新的信息,实现 １＋１＞２ 的效果.随着分子生物学㊁化学合成等技术的发展,特别是纳米材料及技术的应用,多种新型双模态探针如P E T Ｇ光学㊁S P E C T ＧM R I 及M R I Ｇ光学等双模态技术已在逐步发展中,甚至部分成果已用于临床[２Ｇ３].其中,P E T /M R 双模态探针的研究与进展最引人注目.㊀㊀一体化P E T /M R 对M R I 和P E T 成像技术进行整合,所得图像既有M R I 高空间分辨率,高对比度的优势,又有P E T 成像高灵敏度㊁分子水平成像的特点,实现解剖结构显像与功能成像的完美统一.但是传统的正电子显像药物不能充分发挥一体化P E T /M R 空间时间一致性的优势,亟待能够同时被P E T 和M R I 探测到的新型P E T /M R 双模态探针的研发及临床应用转化.本文具体介绍了当前P E T /M R 双模态成像探针的研究现状及应用前景.㊀㊀１㊀P E T /M R 双模态探针㊀㊀P E T/M R 双模态探针一般由两部分组成,一部分是M R I 成像组分,如金属钆㊁铁等;另一部分是４７１L a b e l e d I mm u n o a s s a ys&C l i n M e d ,J a n ．２０２１,V o l ．２８,N o ．１P E T示踪组分,如１８F㊁６４G u等.有些探针可能还含有靶向基团,如多肽㊁蛋白㊁抗体等.根据其组成结构的差异,大致分为小分子探针和纳米探针.㊀㊀１．１㊀小分子双模态探针㊀㊀G d３＋螯合物是最常用的小分子M R I造影剂(c o n t r a s t a g e n t,C A),其依赖改变T１弛豫来增强对比度.F R U L L A N O等[４]合成了小分子探针G dＧD O T AＧ４A M PＧF,此探针由两部分组成:一部分是基于钆Ｇ１,４,７,１０Ｇ四氮杂环十二烷Ｇ１,４,７,１０Ｇ四羧酸(G dＧD O T A)的M R I成像组分(具有p H响应性,即M R IT１信号强度和弛豫率与p H水平相关),另一部分是P E T 放射性核素１８F.它可作为一种肿瘤的生物标志物从而对肿瘤微环境例如酸碱度进行定量测量.有研究报道了G d３＋和其他螯合剂络合后被一些发射正电子的金属离子所标记(如C u２＋㊁G a３＋㊁I n３＋)[５Ｇ６].挑战在于如何将这些放射性金属离子放置在特定的配位点上.N O T N I等[６]合成小分子P E T/M R探针６８G a T R A P(HM D AＧ[D O T A]ＧG d)３,由于其弛豫性与温度有关,所得为温度响应型P E T/M R探针,实现了智能成像从而进行医学诊断.㊀㊀１．２㊀纳米双模态探针㊀㊀大多数P E T/M R双模态探针都是基于纳米颗粒(n a n o p a r t i c l e s,N P s)构建而成.这是因为小分子其负载能力有限而难以携带多个成像报告分子甚至靶向基团.纳米颗粒因其特殊的体积及结构使其具有一些特殊性质,例如表面可修饰性强㊁低毒性㊁催化能力高以及不易受体内和细胞内各种酶降解等,这些优点允许其同时携带多种基团[７Ｇ８].现如今已经开展了多种基于N P s的P E T/M R双模态探针的临床前研究,根据纳米材料的化学成分,N P可以大致分为有机纳米颗粒和无机纳米颗粒两类.㊀㊀１．２．１㊀基于无机纳米材料的P E T/M R双模态探针㊀㊀该类别中最常用的载体是氧化铁纳米颗粒(i r o n o x i d e n a n o p a r t i c l e s,I O N P),其核心由磁铁矿(F e３O４)和(或)磁赤铁矿(γＧF e２O３)组成,能够缩短T２弛豫时间引起M R I信号变化.I O N P拥有生物相容性好㊁低毒性及表面修饰方便易行等优点,一些I O N P 已被美国食品药品监督管理局(F D A)和欧洲委员会批准为M R I造影剂,有良好的临床应用前景.其中,超顺磁性氧化铁(s u p e r p a r a m a g n e t i c i r o no x i d e, S P I O)最为常见,有许多研究将之与P E T示踪剂结合,构建的P E T/M R探针已成功用于肿瘤成像与诊断㊁药物转运与治疗等多种领域中,是当前P E T/M R双模态探针中的重要研究方向.㊀㊀２００８年J A R R E T T等[９]合成了探针６４C uＧD O T AＧA D I O,这是有关P E T/M R双模态探针的最早科学文献之一.６４C u与双功能螯合剂配位后形成热力学稳定的螯合物,然后缀合至纳米颗粒(A D I O),成功获得探针.后来,MA D R U等[１０]提出了一种新的㊁省时的㊁无螯合剂的偶联方法,即用６４C u直接标记聚乙二醇(P E G)的S P I O N s构建探针,通过P E T/M R 成像实现C５７B L/６J小鼠前哨淋巴结(s e n t i n e l l y m p hn o d e s,S L N s)的定位.近年来为了提高探针的靶向性,有研究通过在探针上连接一些靶向基团增强其主动靶向的能力[１１].K I M等[１２]使用齐墩果酸(O A)作为肿瘤靶向分子,构建探针６８G aＧN O T AＧO AＧI O N P注射入结肠癌(H TＧ２９)的B A L B/c裸鼠模型中,结果显示癌细胞高摄取该探针,且探针的积累抑制了结肠癌细胞增殖.此探针不仅实现了肿瘤显像,还起到了抑制肿瘤的作用,实现诊疗一体化.㊀㊀尽管如此,I O N P具有一些难以忽视的缺点.首先,它们起阴性对比作用,在给药后T２信号降低使得医学评估不那么容易.而且,高的磁化率会导致失真伪影,并降低对比度和信噪比.所以其他类型的磁性纳米材料开始被大家研究,基于二氧化硅的N P被认为是整合成像探针的理想生物相容性基质.主要分为两类:固体二氧化硅纳米颗粒(S i N P)和介孔二氧化硅纳米颗粒(M S N).S i N P被广泛用作光学显像剂,而M S N通常被用于C T㊁M R I㊁P E T 和多模态成像[１３].M S N具有诱人的特性:它的表面积极大,大小㊁形态和孔隙皆可调,并易于进行功能化修饰[１４].在双模态P E T/M R成像中,M S N常用作金属N P的涂层材料或直接作为显像组分的载体.㊀㊀B U R K E等[１５]用一种新颖的简便的方法来制备P E T/M R双模态探针,即在二氧化硅涂层的氧化铁纳米棒上涂覆P E G和/或四氮杂大环(D O３A),用６８G a进行放射性标记.研究表明,在存在二氧化硅涂层的情况下,制备高稳定性放射性纳米探针不需要大环螯合剂.HU A N G等[１６]报道了一种基于M S N的三模态成像纳米探针,用于定位和追踪肿瘤转移性前哨淋巴结(TＧS L N s).在该系统中,通过不同的偶联策略将三种成像组分包括近红外(N I R)染料Z W８００㊁T１C A G dＧD T T A和放射性核素６４C u整合到M S N中.体内外实验均证实了纳米探针的高稳定性,表明M S N探针定位S L N和鉴定肿瘤转移的可行性.５７１标记免疫分析与临床㊀２０２１年１月第２８卷第１期㊀㊀１．２．２㊀基于有机纳米材料的P E T/M R双模态探针㊀㊀近十年,有机纳米材料例如脂质体㊁树状聚合物㊁聚合物胶束和蛋白质等在肿瘤的诊断中扮演着重要的角色,因可以作为载体平台携带多种成像基团,如放射性核素㊁N I R F染料及M R I造影剂等而具有成为多模态成像探针的巨大潜力.㊀㊀脂质体(l i p o s o m e,L P)是由两亲性磷脂组成的囊泡,故亲水性分子可封装于内部的水性隔室,而疏水性分子插入脂质壳中.脂质体具有良好的生物相容性,无毒且可生物降解,也极易修饰,这些特性使之成为整合成像基团的极佳平台.M I T C H E L L 等[１７]制备了具有不同长度短乙二醇基(nＧE G)的脂质体制剂,通过脂质体头部中的螯合剂(D O T A)螯合G d３＋用于M R I,螯合１１１I n用于S P E C T,螯合６４C u 用于P E T,从而获得多模态成像探针.A B O U等[１８]用放射性核素８９Z r标记了顺磁L P,并与奥曲肽偶联,通过人类生长抑素受体亚型２(S S T R２)选择性靶向神经内分泌肿瘤.由于放射性金属对脂质磷酸根基团的亲和力,实验采用了无螯合剂策略.所得P E T/MR图像可显示清晰的肿瘤.㊀㊀胶束(m i c e l l e)是表面活性剂在溶液中的浓度到达及超过临界胶束浓度(C M C)后,其分子或离子自动缔合成的胶体大小的聚集体质点微粒.像脂质体一样,胶束也具有核/壳结构的特征,是具有疏水核和亲水壳的自组装胶体纳米颗粒.在药物开发上,胶束已成功地用作与水不溶性药物的载体.而近来高分子胶束由于其高稳定性和良好的生物相容性在肿瘤成像方面也越来越受到关注.通过将水溶性共聚物与脂质(例如聚乙二醇Ｇ磷脂酰乙醇胺, P E GＧP E)缀合,可以合成一组特殊的聚合物胶束,修饰的胶束能够在表面上携带各种基团,从而构建出多模态成像探针.T R U B E T S K O Y等[１９]将钆Ｇ二乙烯三胺五乙酸Ｇ磷脂酰乙醇胺(G dＧD T P AＧP E)和１１１I nＧ二乙烯三胺五乙酸Ｇ硬脂胺(１１１I nＧD T P AＧS A)掺入２０n m P E GＧP E胶束中,然后皮下注射到兔的爪中,使用伽玛闪烁显像和M R I成像采集相应的局部淋巴管图像.S T A R M A N S等[２０]研发了一种P E T/M R 成像探针即８９Z r/F eＧD F OＧ胶束,借助高渗透长滞留效应(e n h a n c e d p e r m e a b i l i t y a n dr e t e n t i o ne f f e c t,E P R),体内P E T/M R图像可清晰显示肿瘤.然而,脂质体和胶束都不稳定,特别是在血清中,因而有一些研究通过交联它们以实现更好的稳定性[２１Ｇ２３].㊀㊀树枝状聚合物是一组具有树状内部结构的高度支化的球形聚合物.通过控制聚合度,可以改变各种尺寸㊁分子量.树枝状聚合物可以把造影剂或药物封装在其内部空间或锚定在表面上,是构建多模态成像探针的理想平台.迄今为止,开展了很多基于树枝状聚合物的P E T探针研究,而基于树枝状聚合物的双模态探针却多是MR I/荧光㊁光学/P E T㊁C T/M R I等[２４Ｇ２５],关于P E T/M R探针的研究仍有待开展.㊀㊀后来,仿生方法在科学界引起一波热潮,许多科学家正试图模仿体内自然发生的现象,以便获得更具生物相容性和可生物降解的材料用于医疗.仿生方法的关键在于修饰天然存在的生物聚合物以降低探针免疫原性并提高探针效能.海藻酸盐㊁透明质酸㊁壳聚糖等生物聚合物以及铁蛋白㊁脂蛋白和病毒衣壳作为探针载体平台引起了人们的研究[２６]. V E C C H I O N E等[２７]提出了一个完全生物相容的平台用于P E T/M R成像.他们用壳聚糖和透明质酸制成的核Ｇ壳纳米载体截留了G dＧD T P A,将探针弛豫特性提高了５倍,同时吸附了１８FＧ脱氧葡萄糖(１８FＧF D G),而没有对两个F D A批准的C A进行任何修饰.F A N等[２８]制备了水溶性黑色素纳米颗粒(MN P),MN P不仅可以提供其用于光声成像(P A I)的固有光学特性,而且还可以与金属离子(６４C u２＋㊁F e３＋)有效地螯合用于P E T和M R I成像.㊀㊀２㊀P E T/M R双模态探针的应用㊀㊀迄今多数P E T/M R双模态探针仍处于动物实验阶段,因双模态可以提供多维度的信息其临床转化,应用前景将非常广阔,其显像优势主要集中于肿瘤病学㊁心脏病学及神经病学等领域,成为诊断疾病和指导治疗的有效手段.㊀㊀２．１㊀在恶性肿瘤中的应用㊀㊀肿瘤在出现临床症状前就已在微观分子㊁细胞水平上发生了功能和结构的改变,P E T/M R双模态探针结合P E T和M R I的优势,可获得较全面的病变部位的信息,无疑是肿瘤早期诊断㊁分期㊁监测进展及疗效评价的新手段.B U C H B E N D E R等[２９Ｇ３０]发现在肿瘤T NM分期中,P E T/M R相比P E T/C T 可提供更高的准确性;病变在需要较高的软组织对比时P E T/M R发挥了重要作用.㊀㊀肿瘤的微环境也是影响肿瘤发生发展的重要因素,已有学者通过研究表明P E T/M R双模态显像可反映肿瘤血管生成㊁细胞凋亡及受体生成等过程[３１Ｇ３２].淋巴结转移是恶性肿瘤分期和治疗的重要标志,前面所述的研究[１０,１６]已利用多模态探针进行６７１L a b e l e d I mm u n o a s s a y s&C l i n M e d,J a n．２０２１,V o l．２８,N o．１P E T/MR成像,实现了前哨淋巴结的定位,提高前哨淋巴结精准成像技术,有望改善癌症治疗的术前计划和术中指导.㊀㊀２．２㊀在心血管疾病中的应用㊀㊀心血管疾病一直以来都是引起中老年人死亡的主要原因之一,往往病情凶险,而治疗策略和预后评估方法有限,尽早识别诊断尤为重要.现已发现心脏P E T/M R在诊断心肌缺血㊁心肌梗死㊁心肌炎㊁结节病㊁心脏肿瘤等方面具有独特的优势[３３Ｇ３４].此外,有研究表明P E T/M R在动脉粥样硬化斑块的鉴定中也有一定的潜力.J A R R E T T等[３５]构建６４C uＧMＧB S A 探针清楚显示了斑块内巨噬细胞的分布;S U等[３６]合成６８G aＧN G DＧM N P探针反映了斑块内病理性血管生成的过程,P E T/M R实现了易损斑块的可视化.通过非侵入性的影像学方法在症状出现前早期诊断,有助于预防动脉粥样硬化相关疾病.㊀㊀２．３㊀在神经病学方面的应用㊀㊀M R I和P E T在神经系统疾病的诊断中一直起着重要作用.研究表明,从P E T/M R获得的综合数据更有助于估计脑肿瘤范围,进行肿瘤分级及判断是否复发[３７Ｇ３８].此外,已发现P E T/M R在改善许多神经退行性疾病的早期诊断和鉴别诊断方面具有巨大但尚未开发的潜力[３８Ｇ３９].G A R I B O T T O等[４０]在１５例神经退行性疾病患者中验证了P E T/M R显像的可行性及优越性.新型的P E T示踪剂,即将放射性核素与βＧ淀粉样蛋白,t a u或αＧ突触核蛋白聚集体结合,将为P E T与M R I的结合提供了更多的可能,目前还尚无该类双模态探针,它的研发将会有巨大的前景.㊀㊀３㊀挑战与展望㊀㊀随着分子影像学的发展及与其他技术间跨学科的交叉研究,多模态显像正逐步从动物显像研究转向临床诊疗实践.其中基于纳米颗粒的P E T/M R 双模态成像探针更是当前研究热点,然而研究还处于起步阶段,许多困难仍有待解决.首先,纳米材料在体内的生物安全性是影响其临床转化的关键性问题,潜在的生物毒性还需进一步研究;其次,纳米探针制备过程复杂,如何将两种成像报告分子和靶向基团连接到单一纳米粒,如何改善探针的尺寸㊁水溶性及生物相容性等还需进一步解决;最后,不同成像基团在体内具有不同的代谢过程和体内半衰期,特别是一些短半衰期放射性核素(如６８G a)与纳米颗粒在体内的药代动力学不匹配,如何精准调控它们的体内行为实现协同还面临巨大挑战.㊀㊀未来P E T/M R双模态探针的发展,一个重要的方向是 诊疗一体化 ,即同时用于诊断和治疗.如将化疗药物顺铂装载在脂质体或S P I O中,该类探针不仅可以早期检测肿瘤,还可以对肿瘤进行靶向治疗.总之,P E T/M R双模态成像探针有望改变我们现有的疾病诊断㊁治疗方法,提供关于疾病准确和全面的信息,实现个体化治疗.参考文献[１]W E I S S L E D E RR,P I T T E T M J．I m a g i n g i n t h e e r a o f m o l e c u l a r o n c o l o g y[J]．N a t u r e,２００８,４５２(７１８７):５８０Ｇ５８９．[２]黄佳国,曾文彬,周明,等．双模态分子影像探针研究进展[J]．生物物理学报,２０１１,２７(４):３０１Ｇ３１１．[３]杨卫东,张明如．多模态分子探针的研究进展[J]．功能与分子医学影像学杂志(电子版),２０１６,５(２):９４４Ｇ９４８．[４]F R U L L A N O L,C A T A N A C,B E N N E R T,e ta l．B i m o d a l M RＧP E Ta g e n t f o r q u a n t i t a t i v e p Hi m a g i n g[J]．A n g e w C h e m I n tE dE n g l,２０１０,４９(１３):２３８２Ｇ２３８４．[５]V O L O G D I N N,R O L L A G A,B O T T A M,e t a l．O r t h o g o n a l s y n t h e s i s o f ah e t e r o d i m e r i c l i g a n df o r t h ed e v e l o p m e n to f t h eG d(I I I)ＧG a(I I I)d i t o p i cc o m p l e xa sa p o t e n t i a l p HＧs e n s i t i v eM R I/P E T p r o b e[J]．O r g B i o m o l C h e m,２０１３,１１(１０):１６８３Ｇ１６９０．[６]N O T N IJ,H E R MA N N P,D R E G E L Y I,e ta l．C o n v e n i e n t s y n t h e s i s o f(６８)G aＧl a b e l e d g a d o l i n i u m(I I I)c o m p l e x e s: t o w a r d s b i m o d a l r e s p o n s i v e p r o b e s f o r f u n c t i o n a l i m a g i n g w i t h P E T/M R I[J]．C h e m i s t r y,２０１３,１９(３８):１２６０２Ｇ１２６０６．[７]Y A N GCT,G H O S H KK,P A D M A N A B H A NP,e t a l．P E TＧM Ra n d S P E C TＧM R m u l t i m o d a l i t yp r o b e s:D e v e l o p m e n ta n dc h a l l e n g e s[J]．T h e r a n o s t i c s,２０１８,８(２２):６２１０Ｇ６２３２．[８]L AM BJ,HO L L A N DJP．A d v a n c e dm e t h o d s f o r r a d i o l a b e l i n g m u l t i m o d a l i t y n a n o m e d i c i n e s f o rS P E C T/M R I a n dP E T/M R I[J]．J N u c lM e d,２０１８,５９(３):３８２Ｇ３８９．[９]J A R R E T TBR,G U S T A F S S O N B,K U K I SDL,e t a l．S y n t h e s i s o f６４C uＧl a b e l e dm a g n e t i c n a n o p a r t i c l e s f o rm u l t i m o d a l i m a g i n g[J]．B i o c o n j u gC h e m,２００８,１９(７):１４９６Ｇ１５０４．[１０]M A D R U R,B U D A S S IM,B E N V E N I S T E H,e t a l．S i m u l t a n e o u s p r e c l i n i c a l p o s i t r o n e m i s s i o n t o m o g r a p h yＧm a g n e t i cr e s o n a n c e i m a g i n g s t u d y o f l y m p h a t i c d r a i n a g e o f c h e l a t o rＧf r e e(６４)C uＧl a b e l e d n a n o p a r t i c l e s[J]．C a n c e rB i o t h e r R a d i o p h a r m,２０１８,３３(６):２１３Ｇ２２０．[１１]B IY,H A O F,Y A N G,e t a l．A c t i v e l y t a r g e t e dn a n o p a r t i c l e s f o r d r u g d e l i v e r y t o t u m o r[J]．C u r rD r u g M e t a b,２０１６,１７(８):７６３Ｇ７８２．[１２]K I MSM,C H A E M K,Y I M MS,e t a l．H y b r i dP E T/M R i m a g i n g o f t u m o r su s i n g a no l e a n o l i ca c i dＧc o n j u g a t e dn a n o p a r t i c l e[J]．B i o m a t e r i a l s,２０１３,３４(３３):８１１４Ｇ８１２１．[１３]V I V E R OＧE S C O T OJL,HU X F O R DＧP H I L L I P SRC,L I N W．S i l i c aＧb a s e dn a n o p r o b e s f o rb i o m e d i c a l i m a g i n g a n dt h e r a n o s t i c７７１标记免疫分析与临床㊀２０２１年１月第２８卷第１期a p p l i c a t i o n s[J]．C h e mS o cR e v,２０１２,４１(７):２６７３Ｇ２６８５．[１４]C H A B G,K I M J．F u n c t i o n a lm e s o p o r o u ss i l i c an a n o p a r t i c l e s f o rb i oＧi m a g i n g a p p l ic a t i o n s[J]．W i l e y I n t e rd i s c i p Re vN a n o m e dN a n o b i o t e c h n o l,２０１９,１１(１):e１５１５．[１５]B U R K EBP,B A G H D A D IN,K O W N A C K A A E,e t a l．C h e l a t o r f r e e g a l l i u mＧ６８r a d i o l a b e l l i n g o f s i l i c a c o a t e d i r o n o x i d e n a n o r o d s v i a s u r f a c e i n t e r a c t i o n s[J]．N a n o s c a l e,２０１５,７(３６):１４８８９Ｇ１４８９６．[１６]HU A N G X,Z H A N GF,L E ES,e t a l．L o n gＧt e r m m u l t i m o d a l i m a g i n g o f t u m o r d r a i n i n g s e n t i n e l l y m p hn o d e su s i n g m e s o p o r o u s s i l i c aＧb a s e d n a n o p r o b e s[J]．B i o m a t e r i a l s,２０１２,３３(１７):４３７０Ｇ４３７８．[１７]M I T C H E L LN,K A L B E RTL,C O O P E R MS,e t a l．I n c o r p o r a t i o n o f p a r a m a g n e t i c,f l u o r e s c e n ta n dP E T/S P E C Tc o n t r a s ta g e n t s i n t o l i p o s o m e s f o rm u l t i m o d a l i m a g i n g[J]．B i o m a t e r i a l s,２０１３,３４(４):１１７９Ｇ１１９２．[１８]A B O UDS,T H O R E K DL,R A M O SN N,e t a l．(８９)Z rＧl a b e l e d p a r a m a g n e t i c o c t r e o t i d eＧl i p o s o m e s f o r P E TＧM R i m a g i n g o f c a n c e r[J]．P h a r m R e s,２０１３,３０(３):８７８Ｇ８８８．[１９]T R U B E T S K O YVS,F R A N KＧK A M E N E T S K Y M D,WH I T E M A N K R,e t a l．S t a b l e p o l y m e r i c m i c e l l e s:l y m p h a n g i o g r a p h i c c o n t r a s tm e d i a f o r g a mm a s c i n t i g r a p h y a n dm a g n e t i c r e s o n a n c e i m a g i n g[J]．A c a dR a d i o l,１９９６,３(３):２３２Ｇ２３８．[２０]S T A R MA N SL W E,HUMM E L I N K M,R O S S I N R,e ta l．(８９)Z rＧa n d F eＧl a b e l e d p o l y m e r i c m i c e l l e sf o rd u a l m o d a l i t y P E Ta n dT(１)Ｇw e i g h t e d M R i m a g i n g[J]．A d vH e a l t h cM a t e r,２０１５,４(１４):２１３７Ｇ２１４５．[２１]X I EJ,C H E N K,HU A N GJ,e ta l．P E T/N I R F/M R I t r i p l e f u n c t i o n a l i r o no x i d e n a n o p a r t i c l e s[J]．B i o m a t e r i a l s,２０１０,３１(１１):３０１６Ｇ３０２２．[２２]Z H O U W,Y A N G G,N IX,e t a l．R e c e n t a d v a n c e s i nc r o s s l i n k e d n a n o g e lf o r m u l t i m o d a l i m a g i n g a n d c a n c e r t h e r a p y[J]．P o l y m e r s(B a s e l),２０２０,１２(９):１９０２．[２３]A R Y A LS,K E YJ,S T I G L I A N O C,e ta l．P o s i t r o ne m i t t i n g m a g n e t i c n a n o c o n s t r u c t sf o r P E T/M R i m a g i n g[J]．S m a l l,２０１４,１０(１３):２６８８Ｇ２６９６．[２４]X U H,R E G I N O C A,K O Y AMA Y,e ta l．P r e p a r a t i o na n d p r e l i m i n a r y e v a l u a t i o n o f a b i o t i nＧt a r g e t e d,l e c t i nＧt a r g e t e d d e n d r i m e rＧb a s e d p r o b ef o rd u a lＧm o d a l i t y m a g n e t i cr e s o n a n c e a n d f l u o r e s c e n c e i m a g i n g[J]．B i o c o n j u g C h e m,２００７,１８(５):１４７４Ｇ１４８２．[２５]W E N S,L I K,C A I H,e ta l．M u l t i f u n c t i o n a ld e n d r i m e rＧe n t r a p p e d g o l d n a n o p a r t i c l e sf o rd u a l m o d e C T/M Ri m a g i n g a p p l i c a t i o n s[J]．B i o m a t e r i a l s,２０１３,３４(５):１５７０Ｇ１５８０．[２６]M A H A M A,T A N G Z,W U H,e t a l．P r o t e i nＧb a s e dn a n o m e d i c i n e p l a t f o r m sf o r d r u g d e l i v e r y[J]．S m a l l,２００９,５(１５):１７０６Ｇ１７２１．[２７]V E C C H I O N ED,A I E L L O M,C A V A L I E R EC,e t a l．H y b r i d c o r e s h e l l n a n o p a r t i c l e s e n t r a p p i n g G dＧD T P Aa n d(１８)FＧF D G f o r s i m u l t a n e o u s P E T/M R I a c q u i s i t i o n s[J]．N a n o m e d i c i n e(L o n d),２０１７,１２(１８):２２２３Ｇ２２３１．[２８]F A N Q,C H E N GK,HUX,e t a l．T r a n s f e r r i n g b i o m a r k e r i n t o m o l e c u l a r p r o b e:m e l a n i nn a n o p a r t i c l e a s an a t u r a l l y a c t i v e p l a t f o r m f o r m u l t i m o d a l i t y i m a g i n g[J]．J A m C h e m S o c,２０１４,１３６(４３):１５１８５Ｇ１５１９４．[２９]B U C H B E N D E RC,H E U S N E R T A,L A U E N S T E I N T C,e t a l．O n c o l o g i cP E T/M R I,p a r t１:t u m o r s o f t h e b r a i n,h e a d a n d n e c k,c h e s t,a b d o m e n,a n d p e l v i s[J]．JN u c lM e d,２０１２,５３(６):９２８Ｇ９３８．[３０]B U C H B E N D E RC,H E U S N E R T A,L A U E N S T E I N T C,e t a l．O n c o l o g i c P E T/M R I,p a r t２:b o n e t u m o r s,s o f tＧt i s s u e t u m o r s,m e l a n o m a,a n d l y m p h o m a[J]．JN u c lM e d,２０１２,５３(８):１２４４Ｇ１２５２．[３１]Z H A N G Y,Y A N G Y,C A I W．M u l t i m o d a l i t y i m a g i n g o f i n t e g r i n α(v)β(３)e x p r e s s i o n[J]．T h e r a n o s t i c s,２０１１,１:１３５Ｇ１４８．[３２]L E EH Y,L IZ,C H E N K,e t a l．P E T/M R I d u a lＧm o d a l i t y t u m o r i m a g i n g u s i n g a r g i n i n eＧg l y c i n eＧa s p a r t i c(R G D)Ｇc o n j u g a t e d r a d i o l a b e l e d i r o no x i d e n a n o p a r t i c l e s[J]．J N u c l M e d,２００８,４９(８):１３７１Ｇ１３７９．[３３]S C H I N D L E RTH．C a r d i o v a s c u l a r P E T/M R i m a g i n g:Q u oV a d i s?[J]．JN u c l C a r d i o l,２０１７,２４(３):１００７Ｇ１０１８．[３４]S A N T A R E L L IM F,P O S I T A N O V,M E N I C H E T T I L,e t a l．C a r d i o v a s c u l a rm o l e c u l a r i m a g i n g:n e w m e t h o d o l o g i c a l s t r a t e g i e s[J]．C u r rP h a r mD e s,２０１３,１９(１３):２４３９Ｇ２４４６．[３５]J A R R E T TBR,C O R R E AC,MA KL,e t a l．I nv i v om a p p i n g o f v a s c u l a r i n f l a mm a t i o nu s i n g m u l t i m o d a l i m a g i n g[J]．P L o S O n e,２０１０,５(１０):e１３２５４．[３６]S U T,WA N G YB,H A N D,e t a l．M u l t i m o d a l i t y I m a g i n g o fA n g i o g e n e s i s i n a R a b b i t A t h e r o s c l e r o t i c M o d e lb y G EB P１１P e p t i d e T a r g e t e d N a n o p a r t i c l e s[J]．T h e r a n o s t i c s,２０１７,７(１９):４７９１Ｇ４８０４．[３７]F I N K JR,MU Z I M,P E C K M,e ta l．M u l t i m o d a l i t y B r a i n T u m o r I m a g i n g:M RI m a g i n g,P E T,a n dP E T/M RI m a g i n g[J]．J N u c lM e d,２０１５,５６(１０):１５５４Ｇ１５６１．[３８]M I L L E RＧT H O M A SM M,B E N Z I N G E RTL．N e u r o l o g i c a p p l i c a t i o n s o f P E T/M Ri m a g i n g[J]．M a g n R e s o nI m a g i n g C l i n N A m,２０１７,２５(２):２９７Ｇ３１３．[３９]B A R T H E L H,S C H R O E T E R M L,HO F F MA N N K T,e t a l．P E T/M R i nd e m e n t i a a n do t h e r n e u r o d e g e n e r a t i v ed i s e a s e s[J]．S e m i nN u c lM e d,２０１５,４５(３):２２４Ｇ３３．[４０]G A R I B O T T OV,H E I N Z E RS,V U L L I E MO ZS,e t a l．C l i n i c a l a p p l i c a t i o n s o f h y b r i dP E T/M R I i nn e u r o i m a g i n g[J]．C l i nN u c lM e d,２０１３,３８(１):e１３Ｇe１８．８７１L a b e l e d I mm u n o a s s a y s&C l i n M e d,J a n．２０２１,V o l．２８,N o．１。

磁性氧化铁纳米颗粒及其磁共振成像应用_乔瑞瑞

磁性氧化铁纳米颗粒及其磁共振成像应用_乔瑞瑞

磁性氧化铁纳米颗粒及其磁共振成像应用乔瑞瑞,贾巧娟,曾剑峰,高明远中国科学院化学研究所，北京100190收稿日期：2010-11-26；接受日期：2011-02-18基金项目：“973”计划项目(2011CB935800),国家自然科学基金项目(21003135，81090271，20820102035)通讯作者：高明远，电话：(010)62625212，E-mail ：gaomy@摘要：磁性氧化铁纳米颗粒在磁共振成像方面的应用，已经在全世界范围内得到了广泛的关注，相关研究也被各国科学家高度重视。

目前，磁性氧化铁纳米颗粒正在从早期的基于被动识别的肝部磁共振造影，快速转向基于主动识别的磁共振分子影像应用。

本文将围绕磁性氧化铁纳米颗粒的生物体内应用，着重介绍磁性纳米颗粒的制备及其在疾病诊断，尤其是在肿瘤早期影像诊断方面的研究进展。

关键词：磁性氧化铁纳米颗粒；磁共振；分子影像探针；肿瘤中图分类号：R1,O69DOI ：10.3724/SP.J.1260.2011.00272引言随着纳米科学的发展，纳米材料在生物检测、疾病诊断及疾病治疗等方面均展示出了广阔的应用前景[1]。

在众多的纳米材料中，磁性纳米颗粒(magnetic nanoparticles ，MNPs )以其超顺磁特性在磁共振成像(magnetic resonance imaging ，MRI )中表现出独特的造影剂(contrast agent )功能。

配合以良好的生物安全性、表面可修饰性及其特殊的体内行为，磁性纳米颗粒在生物体内的应用方面展现出巨大的应用价值，并已经成为在生物医学中得到实际应用的最成功的纳米材料之一[2～7]。

到目前为止，全世界有多家公司企业参与了氧化铁纳米颗粒造影剂的研制与开发，并且已有多种商品化产品上市[2,4,6,7]。

例如，Advanced Magnetics 公司(Cambridge ，MA ，USA )在大量的临床数据基础之上，率先推出了基于磁性氧化铁纳米材料的药物GastroMark 誖(ferumoxsil ，口服肠胃制剂)，并于1993年在欧洲获得批准上市；1996年，“美国食品药物管理局”(US Food and Drug Administration,FDA )批准了该公司用于肝部造影的静脉注射制剂Feridex 誖(中文译名菲力磁誖)；2000年，先灵公司用于肝部造影的Resovist 誖(ferucarbotran )在欧洲获得批准上市[8]；随后又出现了淋巴造影剂Combidex 誖(Sinerem 誖)。

磁铁吸力 英语

磁铁吸力 英语

IntroductionMagnetic attraction, an intriguing and fundamental phenomenon in the realm of physics, is a powerful force that arises between magnets or magnetic materials due to their intrinsic magnetic fields. This force, which underpins numerous technological applications and scientific advancements, is governed by intricate principles that extend beyond simple binary attraction or repulsion. This comprehensive analysis delves into the multifaceted nature of magnetic attraction, examining its underlying principles, factors influencing its strength, its manifestations across various scales, and its profound impact on modern technology and scientific research.I. Fundamentals of Magnetic Attraction: The Role of Magnetic Fields and PolesAt the heart of magnetic attraction lies the concept of magnetic fields, generated by moving electric charges or the inherent arrangement of electrons within atoms. A magnet possesses a north (N) pole and a south (S) pole, with the magnetic field lines emerging from the N-pole and terminating at the S-pole. According to Coulomb's law for magnetic forces, like poles repel each other, while unlike poles attract, giving rise to the familiar behavior of magnets attracting or repelling each other depending on their relative orientations.The strength of magnetic attraction between two magnets is determined by several factors, including:1. **Magnetic Moment**: This quantifies the magnet's overall magnetic strength, proportional to the product of its pole strength and the distance between the poles (magnetic length). A larger magnetic moment translates to a stronger magnetic force.2. **Distance**: Magnetic attraction follows an inverse square law, meaning that as the distance between two magnets increases, the attractive force decreases proportionally to the square of the distance. This is mathematically expressed as F ∝ (magnetic moment of magnet 1 × magnetic moment of magnet 2) / (4π× distance^2 × permeability of the medium).3. **Orientation**: The angle between the magnetic moments of the interacting magnets significantly affects the net attractive force. When the magnetic moments are aligned, the force is maximized; when they are orthogonal, the force is zero.4. **Magnetic Permeability**: The ease with which a material allows magnetic flux to pass through it influences the strength of magnetic interactions. Materials with high permeability, such as iron, enhance magnetic attraction, whereas non-magnetic substances like air or vacuum attenuate it.II. Manifestations of Magnetic Attraction Across Different ScalesA. Molecular and Atomic LevelAt the microscopic level, magnetic attraction is rooted in the quantum mechanical behavior of electrons within atoms. Unpaired electrons in certain elements, such as iron, cobalt, and nickel, possess intrinsic magnetic moments due to their spin and orbital motion. When these atoms align their magneticmoments cooperatively, they create a macroscopic magnetic field, giving rise to ferromagnetism, the strongest form of magnetism observed in nature.B. Macroscopic LevelIn everyday life, magnetic attraction is evident in various forms, from simple fridge magnets to complex industrial machinery. Permanent magnets, such as neodymium magnets, maintain a persistent magnetic field due to their stable internal magnetic structure, enabling strong and consistent magnetic attraction. Electromagnets, on the other hand, generate magnetic fields through the flow of electric current, allowing for controllable magnetic attraction.C. Cosmic ScaleMagnetic attraction also plays a significant role in astrophysical phenomena. Earth's magnetic field, generated by the motion of molten iron in its core, not only protects our planet from harmful solar radiation but also guides migrating animals and steers charged particles, creating stunning auroras. Similarly, magnetic fields in stars, galaxies, and even interstellar space influence the dynamics of celestial bodies and the behavior of plasma.III. Applications and Impact of Magnetic Attraction in Technology and ResearchA. Data StorageMagnetic attraction is crucial in modern data storage technologies, such as hard disk drives (HDDs) and magnetic tape. In HDDs, tiny magnetic domains on a spinning platter are polarized to represent digital bits, with the read/write head utilizing magnetic attraction to both record and retrieve data.B. Energy Generation and ConversionMagnetic attraction is central to the operation of electric generators and motors, where it converts mechanical energy to electrical energy and vice versa. In renewable energy systems like wind turbines and hydroelectric generators, the interaction between moving conductors and magnetic fields generates electricity.C. Medical ApplicationsMagnetic resonance imaging (MRI) relies on the interaction between magnetic fields and atomic nuclei, particularly hydrogen, to produce detailed images of internal body structures. Additionally, magnetic nanoparticles are being explored for targeted drug delivery and hyperthermia therapy in cancer treatment, exploiting magnetic attraction for precise localization and controlled release of therapeutic agents.D. Advanced Research and Emerging TechnologiesMagnetic levitation (maglev) trains employ magnetic attraction and repulsion to achieve frictionless movement and high speeds. Moreover, ongoing research in spintronics seeks to harness electron spin and magnetic interactions for novel electronic devices with enhanced functionality and energy efficiency.ConclusionMagnetic attraction, a seemingly simple yet profoundly intricate phenomenon, is governed by the interplay of magnetic fields, pole orientations,distance, and material properties. Its manifestations span across multiple scales, from atomic structures to cosmic phenomena, and have indelibly shaped the course of technological progress and scientific inquiry. As our understanding of magnetism deepens and new applications emerge, magnetic attraction will undoubtedly continue to play a pivotal role in driving innovation and advancing human knowledge.。

磁共振磁敏感成像(SWl)对脑梗塞伴渗血及微出血的诊断价值分析

磁共振磁敏感成像(SWl)对脑梗塞伴渗血及微出血的诊断价值分析

磁共振磁敏感成像(SWl)对脑梗塞伴渗血及微出血的诊断价值分析发表时间：2016-01-20T16:16:43.427Z 来源：《中华医学杂志》2016年1月4期作者：刘连城李猛张学军[导读] 对于患有脑梗塞的患者而言，应对其通过SWI进行检测，此方法能够将脑梗塞伴渗血及微出血患者进行有效检出，同时为患者的后续治疗提供一定的依据。

[摘要]目的：探究磁共振磁敏感成像对脑梗塞伴渗血及微出血患者的诊断价值。

方法：此研究中所选择的40例研究对象均为我院于2014年10月-2015年10月期间收治的脑梗塞患者，对研究对象均进行磁共振常规T1WI、T2WI扫描，同时还应对患者实行DWI以及SWI扫描。

通过统计学软件对其检出率予以比较。

结果：对于疾病检出率而言，SWI的检出率和其他检出率相比较而言，具有一定的准确率，通过统计学软件相比较后结果为P＜0.05，差异显著性较强，因此统计学意义产生。

结论:对于患有脑梗塞的患者而言，应对其通过SWI进行检测，此方法能够将脑梗塞伴渗血及微出血患者进行有效检出，同时为患者的后续治疗提供一定的依据。

[关键词]磁共振磁敏感成像脑梗塞渗血微出血DOI:10.3760/cma.j.issn.0376-2491.2016.04.022作者单位：234000，安徽省宿州市，皖北煤电集团总医院影像科The Value of Magnetic Susceptibility Weighted Imaging (SWl) in the Diagnosis of Cerebral Infarction with Capillary Hemorrhage and Micro HemorrhageLiu Liancheng, Li Meng, Zhang XuejunAbstract: Objective To explore the value of magnetic susceptibility weighted imaging (SWl) in the diagnosis capillary hemorrhage and micro hemorrhage after cerebral infarction. Methods A total of 40 patients with cerebral infarction from October 2014 to October 2015 were retrospectively selected and conducted routine MRI T1WI, T2WI scan. Also, patients should be implemented the DWI and SWI scan. The detection rats of the above methods were studied and compared by statistical software. Results The comparing results indicated by the statistical software showed that comparing with other detection methods, the SWI detection rate is has some accuracy, and the differences between the methods adopted is of statistic significance (P<0.05). Conclusion For patients with cerebral infarction, the SWI detection should be conducted, which can detect patients’ capillary hemorrhage and micro hemorrhage and provide a basis for the subsequent treatment of cerebral infarction patients.Keywords: susceptibility weighted imaging；infarction；ooze blood Microhemorrhage磁敏感度是物质在磁场中所呈现出的一种磁化现象，由于相关因素而致使局部磁场产生相应的不均匀现象，会呈现出一种磁敏感[1]。

靶向药物载体材料羧甲基壳聚糖-聚乙二醇-叶酸的制备与表征

靶向药物载体材料羧甲基壳聚糖-聚乙二醇-叶酸的制备与表征

靶向药物载体材料羧甲基壳聚糖-聚乙二醇-叶酸的制备与表征Li Hailang;Ye Tingxiu【摘要】目的:制备羧甲基壳聚糖-聚乙二醇-叶酸靶向药物载体,开发药物在肿瘤靶向治疗方面的潜在应用价值.方法:采用亲核取代反应,使聚乙二醇两端分别与羧甲基壳聚糖和叶酸耦联,利用1H-NMR对耦合物进行表征,运用1H-NMR积分面积法对耦合物中聚乙二醇-叶酸取代度进行定量.结果:成功制备羧甲基壳聚糖-聚乙二醇-叶酸,耦合物中聚乙二醇-叶酸取代度约为10％.结论:通过亲核取代反应,可以成功制备羧甲基壳聚糖-聚乙二醇-叶酸靶向药物载体材料.【期刊名称】《北方药学》【年(卷),期】2018(015)012【总页数】3页(P136-137,142)【关键词】羧甲基壳聚糖;聚乙二醇;叶酸;靶向药物载体【作者】Li Hailang;Ye Tingxiu【作者单位】;【正文语种】中文【中图分类】R94功能性聚合物纳米粒子可用于药物与基因递送、细胞与组织工程、诊断与治疗等[1～3]。

在这些应用中，通过纳米粒子专一而快速地内化到靶细胞的药物递送领域颇具前景[4～6]。

聚合物纳米粒子不但可以保护生物活性物质还可以促进递送体系中的药物释放[7]。

为进一步改善对肿瘤细胞与癌细胞的靶向作用，本文以叶酸作为靶头分子构建一种水溶性的、生物相容性靶向药物载体材料。

现已证实，肿瘤细胞外膜过量表达叶酸受体，对叶酸具有专一亲和力。

甲壳素是葡萄糖胺与N-乙酰基-D-葡萄糖胺的共聚物，在自然界中的产量仅次于纤维素，去乙酰化后得到壳聚糖。

由于它具有生物可降解性、生物相容性、止血、抑菌以及廉价等特性，壳聚糖已作为生物材料用于药物递送、基因递送以及其他生物医学等[8]。

羧甲基壳聚糖是一种水溶性的壳聚糖衍生物，在该衍生物中原壳聚糖单体结构中羟基上的H原子被羧甲基取代，生物相容性已得到证实[9]。

人类多种肿瘤细胞均过量表达叶酸受体，这为特定药物有效靶向肿瘤细胞提供有力手段[10]。

磁性纳米颗粒MNPs

磁性纳米颗粒MNPs

(scale bar: 10 µm). c) Bio-TEM images of
A549 cells incubated with IONP20-TAT-Tf (i–iii)
Peng H, Tang J, Zheng R, et al. Nuclear-Targeted Multifunctional Magnetic Nanoparticles for Photothermal Therapy.[J].
Applications
1.MRI and imaging applications
The figure shows T2-weighted MR images of dextran coated MNPs with different Fe concentrations. It is shown that the T2-weighted images’ brightness decreases significantly with the increase of Fe concentration. The observation reveals that dextran coated MNPs can be considered as a good MR T2 contrast agent under the T2-imaging sequences.
Applications
Applications
MRI and imaging applications Micro-NMR as point of care device
Targeted drug delivery with MNPs
Hyperthermia
SERS detection combined with magnetic trapping

纳米技术让人们更健康,作文

纳米技术让人们更健康,作文

纳米技术让人们更健康,作文英文回答：Nanotechnology has revolutionized many aspects of our lives, including healthcare. It has the potential to greatly improve our overall health and well-being. One of the ways in which nanotechnology can benefit our health is through targeted drug delivery. Nanoparticles can be designed to specifically target and deliver medications to the affected areas in our bodies, increasing the effectiveness of treatments and reducing side effects. For example, in cancer treatment, nanoparticles can be used to deliver chemotherapy drugs directly to the tumor, minimizing damage to healthy cells.In addition to targeted drug delivery, nanotechnology can also be used for early detection and diagnosis of diseases. Nanosensors can be developed to detect specific biomarkers or molecules that indicate the presence of a disease. This can lead to earlier and more accuratediagnosis, allowing for prompt treatment and better prognosis. For instance, nanosensors can be used to detect the presence of certain proteins in the blood that are indicative of heart disease, enabling early intervention and prevention of further complications.Furthermore, nanotechnology has the potential to improve the effectiveness of medical imaging techniques. Nanoparticles can be used as contrast agents to enhance the visibility of specific tissues or organs in imaging scans. This can aid in the detection and diagnosis of diseases, as well as monitoring the progress of treatments. For example, magnetic nanoparticles can be used in magnetic resonance imaging (MRI) to improve the visualization of tumors or lesions, providing valuable information for treatment planning.Moreover, nanotechnology can play a significant role in regenerative medicine. Nanomaterials can be used to create scaffolds that mimic the natural environment of cells, promoting tissue regeneration. This can be particularly beneficial in the treatment of injuries or diseases thatinvolve the loss or damage of tissues, such as spinal cord injuries or organ failure. By providing a supportive structure for cells to grow and regenerate, nanotechnology can help restore function and improve quality of life.In summary, nanotechnology has the potential to greatly improve our health and well-being. Through targeted drug delivery, early detection and diagnosis, improved medical imaging, and regenerative medicine, nanotechnology offers promising solutions to various healthcare challenges. With continued advancements in nanotechnology, we can expect even more innovative and effective approaches to improving human health.中文回答：纳米技术已经在许多方面改变了我们的生活，包括医疗保健。

《科技英语》课后习题答桉完整版

《科技英语》课后习题答桉完整版

《科技英语》课后习题答桉完整版大学英语的预习好帮手Main Content: UNIT 1 *****TICSText A “Game Theory”科技英语阅读方法“名词化结构”科技英语翻译技巧“名词化结构”Step:II. Language Points大学英语的预习好帮手… he must anticipate and overcome resistance to his plans. (Para.3) anticipate: v. 1) to expect or realize beforehand; to foresee e.g. The experts are anticipating the negative effects of air pollution. anticipate: v. 2) to deal with or use before proper time 预支e.g. Ted was not used to saving monthly and he would always anticipate his income. The essence of a game is the interdependence of player strategies. (Para.4) Paraphrase: The key principal of a game is that player strategies are dependent on each other. essence: n.1) the quality which makes a thing what it is; the inner nature or most important quality of a thing e.g. The two things are the same in outward form but different in essence.essence: n. 2) extract obtained from a substance by taking out as much of the mass as possible e.g. milk essence; essence of peppermint (椒薄荷、椒薄荷油) 椒薄荷、interdependence: n. the quality or fact of depending on each other inter-为前缀，意为between each other, 类似的词还有interchange、intermarry、international、interview 等。

神奇的纳米医学技术阅读及读后感

神奇的纳米医学技术阅读及读后感

神奇的纳米医学技术阅读及读后感英文回答：Nanomedicine: A Revolutionary Advance in Healthcare.Nanomedicine refers to the application of nanotechnology to medicine, leveraging materials and devices at the nanoscale to diagnose, treat, and prevent diseases. This burgeoning field promises unprecedented possibilities for improving healthcare.Nanomedicine Applications in Diagnosis.Nanoparticles can be engineered with specific properties, such as fluorescence or magnetic resonance, to enhance imaging techniques. By targeting specific biomarkers, they enable precise disease detection and monitoring at an early stage. For instance, gold nanoparticles can be used to detect cancer cells in the bloodstream with high sensitivity.Nanomedicine in Targeted Drug Delivery.Nanocarriers, like liposomes and micelles, can encapsulate and deliver drugs directly to diseased cells or tissues. This targeted approach reduces systemic toxicity and enhances therapeutic efficacy. For example, nanoparticle-based delivery systems can improve the bioavailability of poorly soluble drugs or deliver siRNAfor gene silencing in cancer cells.Nanomedicine for Tissue Engineering and Regeneration.Nanomaterials can serve as scaffolds for tissue engineering, providing support for cell growth and tissue repair. They can be engineered to mimic the natural extracellular matrix, promoting cell adhesion, proliferation, and differentiation. This technology holds promise for regenerating damaged tissues and organs, such as in bone regeneration or nerve repair.Benefits of Nanomedicine.Improved Diagnostics: Enhanced imaging techniques enable early disease detection and monitoring.Precise Drug Delivery: Targeted nanocarriers deliver drugs directly to diseased tissues, minimizing side effects and maximizing therapeutic impact.Tissue Regeneration: Nanomaterials provide scaffolds for tissue engineering, facilitating the repair and regeneration of damaged tissues.Personalized Medicine: Nanomedicine allows fortailored treatments based on individual patient characteristics, optimizing therapeutic outcomes.Challenges and Future Directions.While nanomedicine offers immense potential, challenges remain. Concerns include toxicity and environmental impact, which require careful evaluation. Ongoing research focuses on developing biocompatible and biodegradable nanomaterialsto address these issues.Furthermore, nanomedicine holds the promise of revolutionizing healthcare through advancements in drug discovery, personalized medicine, and regenerative therapies. With continued research and development, it is poised to transform the way we diagnose, treat, and prevent diseases, improving patient outcomes and enhancing overall well-being.中文回答：神奇的纳米医学技术。

免疫细胞的磁共振显像技术研究

免疫细胞的磁共振显像技术研究

免疫细胞的磁共振显像技术研究随着科技的发展，人类越来越能够探索自身体内的奥秘。

其中，免疫细胞在人体中扮演着重要的角色。

本文将探讨免疫细胞的磁共振显像技术研究。

1. 免疫细胞的作用免疫细胞，是人体内主要负责免疫防御的细胞之一。

免疫细胞的主要作用就是寻找并杀死身体内的异常细胞，如病毒、癌细胞等。

同时，当人体受到感染后，免疫细胞也会主动搜索并消灭病原体，以保障身体健康。

2. 磁共振显像技术的介绍磁共振显像技术（Magnetic Resonance Imaging，简称MRI）是一种医学影像技术，通过利用核磁共振的原理，可以对人体内部的组织进行成像。

MRI成像具有分辨率高、无辐射、无创伤等优点，因此被广泛应用于医学诊断领域。

3. 免疫细胞的磁共振显像技术研究在过去的几十年里，科学家们通过不断地研究和探索，发现了用MRI对免疫细胞进行成像的方法。

这种方法基于磁性纳米粒子的特性，可以将这些纳米粒子注入免疫细胞中，通过MRI成像技术对纳米粒子进行成像，从而得到免疫细胞的影像。

在这种技术中，科学家们通常会使用超顺磁性纳米粒子（superparamagnetic nanoparticles，简称SPIONs），将其注入免疫细胞中。

由于SPIONs可以在磁场中对原子核进行弹性散射，从而产生磁性共振信号，因此可以通过MRI成像技术对其进行成像，得到免疫细胞的分布、移动和数量等信息。

4. 磁共振显像技术在免疫学研究中的应用通过免疫细胞的磁共振显像技术，科学家们可以实现对免疫细胞在体内的实时跟踪和成像。

这种技术在免疫学研究中具有广泛的应用前景，例如：1）研究免疫细胞在身体内的运动和分布情况，以了解其在疾病发生和发展过程中的作用和变化。

2）通过跟踪靶向纳米粒子注入的免疫细胞的移动轨迹，可以更好地理解免疫系统的功能和调节机制。

3）该技术对于临床治疗出现活细胞的疾病，如移植反应和自身免疫性疾病等，其研究也有着很大的潜力。

总而言之，免疫细胞的磁共振显像技术在免疫学研究中有着广泛的应用前景，其研究成果将有助于解决许多临床上的重要问题。

磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用

磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用

磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用王磊;刘海林【摘要】胰腺癌和胰腺上皮内瘤变的临床早期诊断十分困难,磁性纳米颗粒是一种具有超顺磁特性的新型磁共振增强造影剂,在肿瘤早期诊断方面有巨大的发展潜力.此文就磁性纳米颗粒制备技术的进展及其在胰腺癌诊断中的应用现状和前景作一综述.【期刊名称】《国际消化病杂志》【年(卷),期】2013(033)004【总页数】3页(P227-229)【关键词】磁性纳米颗粒;胰腺癌;诊断【作者】王磊;刘海林【作者单位】200011 上海交通大学医学院附属第九人民医院消化内科;200011 上海交通大学医学院附属第九人民医院消化内科【正文语种】中文磁共振成像(MRI)是临床上常用的一种检查方法，为显示不同组织之间的差异，特别是为了突出病变组织与正常组织之间的差异，可通过使用造影剂来提高MRI的对比度。

目前临床上使用的多为钆造影剂，属顺磁性造影剂，主要缩短T1、T2弛豫时间；而磁性纳米颗粒具有独特的超顺磁性，主要使T2弛豫时间缩短，对T1弛豫时间的影响较小，可产生传统造影剂无可比拟的MRI造影增强效果。

此外，其良好的生物安全性、独特的生物体内行为及代谢途径、表面可修饰性等优点，在肿瘤早期诊断方面显示出巨大的发展潜力。

自20世纪90年代以来，开发了一系列以磁性氧化铁纳米颗粒为核心的新型MRI造影剂，随着合成工艺的不断革新，磁性氧化铁纳米颗粒经历了从被动靶向模式到主动靶向模式的跨越。

1 磁性纳米颗粒制备技术的发展磁性氧化铁纳米颗粒的合成方法包括水相合成法和非水相合成法。

水相合成法主要依赖铁离子的水解实现磁性氧化铁纳米颗粒的制备，包括微乳液法、溶胶—凝胶法、超声化学法、共沉淀法等。

水相合成方法相对简单，但是制备的磁性氧化铁纳米颗粒表面结构相对复杂，尺寸分布相对较宽。

非水相合成法是近年来开发的新型磁性氧化铁纳米颗粒合成工艺，其中主要的高温热分解法是采用高沸点溶剂为反应传热介质，以有机铁化合物的热分解来制备磁性氧化铁纳米晶体。

细胞内自组装钆纳米粒造影剂

细胞内自组装钆纳米粒造影剂

Controlled intracellular self-assembly of gadolinium nanoparticles as smart molecular MR contrast agentsChun-Yan Cao 1,Ying-Ying Shen 2,Jian-Dong Wang 3,Li Li 2&Gao-Lin Liang 11CAS Key Laboratory of Soft Matter Chemistry,Department of Chemistry,University of Science and Technology of China,96Jinzhai Road,Hefei,Anhui 230026,China,2State Key Laboratory of Oncology in South China,Imaging Diagnosis and Interventional Center,Cancer Center,Sun Yat-sen University,651Dongfeng Road East,Guangzhou 510060,China,3Laboratory of Molecular Pathology and Molecular Imaging,Department of Pathology,Nanjing Jinling Hospital,Nanjing University School of Medicine,305Zhong Shan Dong Lu,Nanjing 210002,China.Herein we developed a new ‘‘smart’’Gd-based MR contrast agent (i.e.,1)which is susceptive to furin,a protease overexpressed in tumor.Under the action of furin,1condenses to form dimers (1-Ds)and the latter self-assemble into gadolinium nanparticles (Gd-NPs).Relaxivity of 1-D is more than 2folds of those of 1and magnevist at 1.5T,and 1.4folds of that of 1at 3T.Intracellular condensation of 1in furin-overexpressed MDA-MB-468cells was proven with direct two-photon laser microscopy (TPLM)fluorescence imaging of the cells incubated with the europium analog of 1(i.e.,2).Intracellular Gd-NPs of 1were uncovered and characterized for the first time.MRI of MDA-MB-468tumors showed that 1has enhanced MR contrast within the tumors than that of its scrambled control 1-Scr.Molecular imaging (MI)is a growing research discipline aims at developing and testing novel tools,reagents,and methods to detect unique in vivo ‘‘biochemical signatures’’that differentiate and char-acterize tissues beyond and before their gross anatomical features becoming obvious 1,2.To date,imagingmodalities of MI that most commonly used for extracting molecular information are nuclear,MRI,and optical techniques 3.Among them,MRI has become increasingly popular in experimental MI and clinical radiology because it allows the interrogation of intact,opaque organisms in three dimensions at cellular resolution (,10m m)4.About 35%of all clinical MR scans utilize contrast agents (CAs).In proton MR,gadolinium (Gd 31)-based T 1CAs are used for reducing the spin-lattice relaxation times of nearby water,increasing the signal from these protons,and making the effected voxel seem ‘‘brighter’’in T 1-weighted image.Superparamagnetic iron oxide nanoparticle-based T 2CAs are used to reduce the spin-spin relaxation time of water,make a ‘‘negative’’contrast effect in T 2*/T 2-weighted image 5.In general,T 1-weighted sequences provide images of higher resolution and signal-to-noise ratio than T 2*/T 2-weighted ones and are free of image artifacts.However,due to the low sensitivity of the CAs,high concentration (0.1–0.6mM)of CA is always required for a typical MR scanning and this calls for the design of highly potent molecular CAs for success 6,mon strategy for increasing the longitudinal molar relaxivity (r 1)of T 1CA is to prolong its rotational correlation time (t r i.e.,the tumbling time of the CA in the water bulk).To achieve this goal,Gd-based agents with higher molecular weights such as Gd functionalized polymer,peptide amphiphiles or viral caspid,dendrimer,liposomes,nanoparticles,micelles,zeolites,fullerenes,carbon nanotubes,clays,and quantum dots were prepared and explored 8–12.Nevertheless,these pre-made gadolinium complexes are facing the problem of cell membrane translocation and targeting,besides the difficulty and reproducibility of their fabrications 13.Therefore,design of ‘‘smart’’or ‘‘activable’’MR CAs that modulate their MR properties (e.g.,relaxivities)on site upon molecular target interaction will overcome the shortcomings of MRI from bottom up.Unfortunately,up to date,only a few gadolinium-based smart MR probes have been developed,including those responsive to b -galactosidase or myeloperoxidase 4,14–17.Self-assem-bly,a prevalent and important process in nature 18,provides an easy approach to design ‘‘smart’’MR probes.In brief,it is not difficult for a small molecular probe (i.e.,building block for self-assembly)to overcome the barrier of cell membrane and be delivered to the targeting site inside cell.At the targeting site,the building blocks (i.e.,small molecular probes)‘‘smartly’’start to self-assemble into nano/micro structures with higher molecular weights which are crucial for a T 1CA.Recently,Rao and co-workers developed a biocompatible condensation reaction between 1,2-aminothiol group of cysteine and the cyano group of 2-cyanobenzothiazole (CBT)which could beSUBJECT AREAS:PROTEASES SELF-ASSEMBLY NANOPARTICLESMAGNETIC RESONANCEIMAGINGReceived28August 2012Accepted4December 2012Published 3January 2013Correspondence and requests for materials should be addressed toL.L.(li2@)or G.-L.L.(gliang@)controlled by pH,reduction and protease at such low a concentration as micromolar for self-assembling nanoparticles with diameters ran-ging from 8nm to 170nm in vitro and in cells ing this system,Rao and co-workers have successfully developed the smart MR CAs of first generation which are susceptive to reducing agents (e.g.,glutathione in cells)and have enhanced T 1relaxivity more than 100%20.Inspired by this,herein we designed the second generation of smart molecular MRI CAs which are not only responsive to intra-cellular glutathione (GSH)but also cleavable by intracellular prote-ase furin who is overexpressed in cancer ing this smart CA,we successfully achieved enhanced MRI of MDA-MB-468tumors on nude mice under common clinical field strength (3Tesla).The trans-Golgi protease furin is a kind of protein convertase that plays important roles in homeostasis,and in diseases ranging from Alzheimer’s disease to anthrax and Ebola fever and cancer 21.Several cancers upregulate furin,including non-small-cell lung carcinomas,squamous-cell carcinomas of the head and neck,and glioblastomas 22.Moreover,the increase of furin in tumors correlates with an increase of membrane type 1-matrix metalloproteinase (MT1-MMP),one of furin’s substrates.MT1-MMP activates extracellular pro-MMP2to induce rapid tumor growth and metastasis 23.Thus,overexpression offurin offers people with a useful hint of early development of certain cancers.There is one big advantage for chemists to study furin that it preferentially cleaves Arg-X-Lys/Arg-Arg #X motifs,where Arg is arginine,Lys is lysine,X can be any amino acid residue and #indi-cates the cleavage site 24.Inspired by these,as shown in Fig.1,we designed Acetyl-Arg-Val-Arg-Arg-Cys(StBu)-Lys(Gd-DOTA)-CBT (1)for self-assembling gadolinium nanoparticles (Gd-NPs )under the action of furin in living tumor cells.In brief,1contains a RVRR peptide sequence for furin cleavage and cell membrane translocation,disulfided Cys for supplying the 1,2-aminothiol group for condensation,Lys con-jugated with Gd-DOTA for MRI.After entering cells,the disulfide bond of the Cys motif of 1is reduced by the intracellular GSH and subsequently its RVRR motif is cleaved by furin on the site of this enzyme (i.e.,Golgi body),resulting in the active intermediate 1-Core .Two 1-Core s condense quickly to yield the amphiphilic dimer (i.e.,1-D )which has a hydrophobic macrocyclic core for self-assembling Gd-NPs via p -p stacking among each others.As-formed Gd-NPs should greatly increase the local concentration of Gd inside cells on one hand.On the other hand,the higher molecular weight of the 1-D should have relaxivity enhancement compared with that of 1atanFigure 1|Shematic illustration of a furin-controlled condensation and self-assembly of Gd-NPs in cancer cells.After entering cancer cells,the disulfide bond of probe 1is reduced by GSH and the RVRR peptide sequence is cleaved by furin to yield the active intermediate 1-Core .Two 1-Core s condense to yield amphiphilic dimer 1-D which self-assembles into Gd-NPs at or near the locations of furin in cells (i.e.,Golgi bodies).identical Gd concentration,presumably owing to an increased rota-tional correlation time.In this work,we demonstrated the furin-controlled condensation of1and self-assembly of Gd-NPs in vitro,measured the enhanced relaxivities of the condensation product of1(i.e.,1-D),directly visualized the intracellular condensation of2withTPLM cell imaging,and characterized the Gd-NPs of1inside cellsfor the first time.We also successfully imaged MDA-MB-468tumorson nude mice with this second generation of smart molecular CA(i.e.,1).ResultsSynthesis.We began the study with the synthesis and preparation of five compounds:1and1-Scr,2and2-Scr,and1-D(Fig.2&Supplementary information).The synthesis for these five com-pounds is simple and straightforward(Supplementary infor-mation).Briefly,the Ac-Arg-Val-Arg-Arg-Cys(StBu)-Lys-OH(A)peptide sequence with protection groups was synthesizedwith Solid Phase Peptide Synthesis(SPPS),then coupled withCBT,purified with high performance liquid chromatography(HPLC)to yield B.Deprotection of B yields C after HPLCpurification.Coupling of C with DOTA(OtBu)3yields D andsubsequent deprotection of D with trifluoroacetic acid(TFA)yields E.At pH value of6–7,10equiv.of GdCl3?6H2O chelates with E at room temperature(RT)for3h yields1after HPLCpurification.Synthesis of1-Scr is similar to that of1with Aused for the synthesis of1being replaced by peptide sequenceAc-Arg-Lys-Arg-Cys(StBu)-Arg-Val-OH(F).Syntheses of2and2-Scr are similar to those of1and1-Scr with GdCl36H2O used atthe last steps for the syntheses of1or1-Scr being replaced withEuCl36H2O respectively.Following the literature,we synthesizedNH2-Cys(SEt)-Lys(Gd-DOTA)-CBT(K)20.Reduction of K with4equiv.of tris(2-carboxyethyl)phosphine(TCEP)yields1-Dafter HPLC purification.Furin-controlled condensation of1and self-assembly of Gd-NPs, and nanocharacterizations.To test our hypothesis,we used1for in vitro study.As shown in Fig.3a,after17h incubation of1at100m M and30u C with1nmol/U of furin,we directly injected the incubation mixture into a HPLC system and collected the peaks for matrix-assisted laser desorption/ionization(MALDI)mass spectroscopic analysis.Interestingly,peaks on HPLC traces at retention times of 38.2min(1-D-1,19.8%),39.5min(1-D-2,21.2%),40.5min(1-D-2, 20.0%),and42.8min(1-D-4,13.5%)share an identical molecular weight and were identified as the condensation products of1(i.e.,1-D,Supplementary Fig.S1).Owing to the presence of L-lysine,these four peaks probably represent the four diastereoisomers of1-D that arise from two different ring-closing orientations during the condensation between L-cysteine motif and cyano group of125. These four dimers account for74.5%of the enzymatic products of 1in total.UV-Vis spectrum at500–700nm of the above reaction mixture showed an obvious increase of absorption compared with that of the solution without furin,suggesting the formation of nanostrcutures(Supplementary Fig.S2).Directly taking the above dispersion for scanning electron microscope(SEM)and trans-mission electron microscope(TEM)observation,we uncovered the3-dimensional and2-dimensional depositions of the Gd-NPs of1(Fig.3b&c).The Gd-NPs have uniform spherical shapes and an average diameter of57.1611.9nm.Measurement of longitudinal molar relaxivity(r1).The MR contrast properties of1,1-Scr,and1-D were evaluated in vitro together with commercial CA Gd-DTPA(Magnevist)as control using phosphate buffered phantoms(pH7.4,0.2M).T1-weighted MR phantom imaging of these CAs was conducted on both1.5Tesla (T)and3T MRI scanners(Supplementary Fig.S3–12).Plots of signal intensity versus inversion time give the T1relaxation times of each CAs at certain concentrations.We calculated the longitudinal molar relaxivity(r1)of each CA according to the equation r15g R1/[CA], where the relaxation rate R1is1/T1.As shown in Fig.4a,at1.5Tand Figure2|Chemical structures of the five designed probes.1,1-Scr,and1-D are Gd-based T1MR CAs.1is susceptive to furin,while1-D is the condensation product of1after furin cleavage.1-Scr is the scrambled control probe of1.2is the Eu analog of1for TPLM cell imaging.2-Scr is the Eu analog of1-Scr.RT,the r 1s were determined to be 6.00s 21mM 21for 1,7.42s 21mM 21for 1-Scr ,and 13.24s 21mM 21for 1-D respectively.Relaxivities of Magnevist at this condition were determined to be 5.39s 21mM 21,which agree well with those reported in literature 26.The relaxivity of 1-D at 1.5T (13.24s 21mM 21)is 2-fold more than that of 1,and comparable to those protein-bound Gd-DOTA analogues reported by Caravan et al 27.Measurement of the relaxivities of abovemen-tioned MR CAs at 3T is shown in Fig.4b.Similar to those at 1.5T,1-D has the highest relaxivity and that of Magnevist is the lowest.In general,relaxivities of these MR CAs at 3T are lowerthan those at 1.5T.All the data of their relaxivities at 1.5T or 3T are summarized in Table 1.Direct imaging furin-controlled intracellular condensation of 2with TPLM .As the Eu-analog of 1,2has all the necessaries for furin-controlled intracellular condensation.Luminescence of europium enables this intracellular process of 2visible under a TPLM.Before applying 2or 2-Scr for TPLM cellular imaging,we tested the expression level of furin in human breast cancer cell line MDA-MB-468with western blot and immunofluorescencestaining.Figure 3|Characterizations of furin-controlled condensation and self-assembly of Gd-NPs of 1in vitro .(a)Upper,HPLC trace of 1in water;lower,HPLC trace of the incubation mixture of 1at 100m M after incubation with 1nmol/U of furin at 30u C for 17h.(b)SEM and (c)TEM images of the Gd-NPs of 1in the above incubationmixture.Figure 4|T 1relaxivity measurements of 1,1-Scr and 1-D.Spin-lattice 1/T 1relaxation rates of 1,1-Scr ,and 1-D at different concentrations in phosphate buffer (pH 7.4,0.2M)at 1.5T (a)and 3T (b),compared to the commercially available MR CA (Magnevist).Relaxivity rates r 1were obtained by comparing the measured (symbols)and theoretical (lines)values.Human colon carcinoma LoVo cells were chosen as control cell lines for western blot study because they are reported to be furin-deficient 28.The protein cell lysates prepared from these two cell lines were analyzed with western ing glycolytic enzyme glyceraldehydes phosphate dehydrogenase (GAPDH)as control,as shown in Fig.5a,MDA-MB-468cells revealed a positive signal forfurin while very weak signal of furin was detected in LoVo cells.Quantification of the western blot signals with image J (NIH,USA)indicated that furin in MDA-MB-468cell has an expression level of 96.2%of GAPDH while that in LoVo is 24.5%of GAPDH (4-fold,p 50.008)(Fig.5b).High expression of furin in MDA-MB-468cells was also confirmed with immunofluorescence staining of furin using rhodamine-labelled secondary antibody (Fig.5c).An overlay of the fluorescence staining of furin with that of nucleus staining (4’,6-diamidino-2-phenylindole,DAPI staining)clearly shows that the locations of furin (i.e.,the Golgi bodies)as reported (Fig.5d)21.TPLM imaging of MDA-MB-468cells incubated with 2at 100m M for 8h shows strong fluorescence signals similar to those in Fig.5c (Fig.5e &Supplementary Movie S1),suggesting 2was under the action of furin and trapped at/near the locations offurin.Table 1|T 1relaxivities (r 1,s 21mM 21)of contrast agents studied at RT and different field strengthsMR field strength [T]11-D Change [%]1-ScrMagnevist 1.5 6.0013.241217.42 5.3935.487.68407.004.10Figure 5|Expression of furin in MDA-MB-468cells and two-photon laser microscopy images of MDA-MB-468cells incubated with 2or 2-Scr.Western blot analysis (a)and quantification (b)of furin in MDA-MB-468cells and LoVo cells.Furin was highly expressed in MDA-MB-468cells (96.2%of GAPDH)while in LoVo cells it was less expressed (24.5%of GAPDH,4-fold,p 50.008).(c,d)Immunofluorescence staining of MDA-MB-468cells with rhodamine-labeled antibody against furin:DsRed channel (red,furin)(c);merged image with DAPI (blue,nucleus)(d).Scale bar:20m m.(e,f)TPLM images (l ex 5725nm,l em 5565–636nm)of MDA-MB-468cells incubated with 2(e)or 2-scr (f)at 100m M for 8h and then rinsed and fixed prior to imaging.Scale bar:20m m.Interestingly,TPLM imaging of MDA-MB-468cells incubated with 2-Scr at same condition only exhibits uniform,weak fluorescence signals(Fig.5f).Self-assembly of Gd-NPs of1in MDA-MB-468cells.After validation of the intracellular condensation of2upon furin cleavage in MDA-MB-468cells,we used electron microscope(EM) to localize the Gd-NPs self-assembled from the condensation products of1incubated with the cells.Cells treated with1-Scr were studied in parallel because1-Scr is inactive to furin.Before EM observation,furin protein expression in the cells was quantified with western blot after8h incubation of the cells with the probes.Unexpectedly,as shown in Fig.6a,after8h incubation with1at100m M,furin protein expression in MDA-MB-468cells exhibits an obvious decrease compared with that in the cells untreated.Quantification of the western blot signals indicated that furin protein in cells treated with1has an expression level of41.7%of GAPDH while that in cells untreated is93.9%of GAPDH(2.3-fold, p50.001)(Fig.6b).In contrast,cells treated with1-Scr did not show decreased expression level of furin protein,compared with that in cells untreated(Supplementary Fig.S13).After8h incubation with1 or1-Scr,the cells were fixed with2.5%glutaraldehyde and thin sections of cells were cut and mounted on copper grids for EM observation.For MDA-MB-468cells that treated with1,large area of clustered Gd-NPs at/near the sites of Golgi bodies were clearly observed(Fig.6c).High magnification of the EM image indicated that these intracellular Gd-NPs of1have an average diameter of24.0 62.3nm(Fig.6d),much smaller than those formed in vitro (Fig.3b).In contrast,there are no Gd-NPs presented in MDA-MB-468cells treated with or without1-Scr(Supplementary Fig. S14&15).MRI of MDA-MB-468tumors with1.Having shown that1 selectively condenses and self-assembles into Gd-NPs in furin-overexpressed MDA-MB-468cells,coronal MR images of mice with subcutaneous MDA-MB-468cell xenografts were acquired precontrast and at various times after the first intravenous(i.v.)injections of1(1st injection:0.15mmol/kg at0min;2nd injection: 0.15mmol/kg at50min)(Fig.7a&b and Supplementary Fig.S16).In the precontrast images(i.e.,0min),there was little intrinsic contrast between the implanted MDA-MB-468tumors and surrounding muscle.At50min following the administration of the1st dose of 1,significantly increased enhancement was observed within the MDA-MB-468tumors(49.1%increase of grey value compared to that at0min).By90min(i.e.,40min after the2nd dose of injection), slightly enhanced signal to that at50min could be observed(53.9% increase of grey value compared to that at0min),and by240min the signal within the tumors remained obvious(20.5%increase of grey value compared to that at0min,Supplementary Fig.S16).To assess specificity of1,control experiments were performed by two i.v. injections of1-Scr into mice with subcutaneous MDA-MB-468cell xenografts at the exactly same doses and time points to those of1.In these animals,enhancement in contrast signal within tumors was also observed.However,at each of the time points studied,the signal was clearly lower than that of mice injected with1(Fig.7a). Quantitative analysis of the MR images is presented in Fig.7b.These results indicated that1is obviously better than1-Scr as a MR CA for imaging MDA-MB-468tumors,probably that1is susceptive to furin while1-Scr is not.Since furin protein levels were decreased in MDA-MB-468cells in vitro treated with1(Fig.6a&b),we also quantified furin protein expression in MDA-MB-468tumors in vivo with western blot after MRI.As shown in Fig.7c,after240min of MRI, expression level of furin in MDA-MB-468tumors treated with1 exhibited an obvious decrease compared with that in control groups.In contrast,expression of furin in tumors treated with1-Scr did not show obvious change compared with that in control groups.Quantification of the western blot signals indicated that furin in tumors of mice injected with1has an expression level of 54.8%of GAPDH while that in tumors of mice untreated is90.9%of GAPDH(1.7-fold,p50.002)(Fig.7d).Furin in tumors of mice injected with1-Scr has an expression level of106.3%of GAPDH, no obvious difference from that in tumors of mice untreated(p5 0.08).To directly observe furin expression levels,after240min of MRI,the tumors were excised for immunofluorescence stainingand Figure6|Expression of furin in MDA-MB-468cells before and after incubation with1,and electron microscopy images of the cells after8h incubation with1.Western blot analysis(a)and quantification(b)of furin expression levels in MDA-MB-468cells before and after incubation with1at 100m M for8h.Expression of furin in cells treated with1has an obvious decrease(41.7%of GAPDH),compared with that in cells untreated(93.9%of GAPDH,2.3-fold,p50.001).Low(c)and high(d)magnification Electron microscopic images of MDA-MB-468cells after incubation with1at100m M rge area of clustered Gd-NPs of1were found at/near Golgi bodies.Scale bar in c:2m m.Scale bar in d:400nm.imaging.The results are shown in Fig.7e.Unlike those of mice injected with or without 1-Scr which show connective red fluorescence signal (i.e.,staining of furin)among the nucleuses (DAPI staining),tumor sections of mice injected with 1exhibited disconnected,attenuated red signal,which also indicates the down regulation of furin protein level by the probe.Although the furin protein itself has lower expression in mice injected with 1,ICP-MS analysis indicated that at 240min after the first injection of 1,tumors on mice have an average Gd content of 0.12m g/g,2.6-fold high of that of tumors treated with 1-Scr (0.046m g/g)(Supplementary Table S1),suggesting that 1is a very potent probe for imaging MDA-MB-468tumors in vivo .Other organs (lung,liver,spleen,and kidney)except brain in mice treated with 1,all exhibit higher contents of Gd than those treated with 1-Scr (Supplementary Table S1).Hematoxylin and eosin (HE)staining of the tissue slices of micetreated with 1or 1-Scr did not show pathologic changes compared with those of mice untreated,suggesting that the doses of 1or 1-Scr herein injected for MRI did not result in toxicity to the mice within the time window of imaging (Supplementary Fig.S17).Discussion1-Scr is an isomer of 1but with a scrambled peptide sequence which could not be cleaved by pound 2is the europium (Eu)analog of 1.We designed 2to evaluate the cell permeability and demonstrate the intracellular condensation of 1by directly imaging the intracellular behavior of 2with TPLM because 2has lumin-escence emissions at 594nm and 616nm when excited with two-photon excitation at 725nm (Supplementary Fig.S18).In parallel,we synthesized 2-Scr to mimic the intracellular behavior of 1-Scr with TPLM imaging.Since the majorities of thecondensationFigure 7|In vivo imaging MDA-MB-468tumors with 1.(a)Representative coronal MR images of mice with subcutaneously xenografted MDA-MB-468tumors at 0min,50min,and 90min after two intravenous injections of 1(upper)or 1-Scr (lower)via tail veins (1st injection:0.15mmol/kg at 0min;2nd injection:0.15mmol/kg at 50min).Tumors are indicated by arrows.(b)Quantitative analysis of grey values of tumor MR images at various time.(c)Western blot analysis and (d)quantification of furin expression in MDA-MB-468tumors on mice injected with 1,with/without 1-Scr after 240min of MRI.Furin protein in tumors of mice injected with 1has a decreased expression level of 54.8%of GAPDH,compared with that in tumors on mice untreated (90.9%of GAPDH,1.7-fold,p 50.002).Expression of furin protein in tumors of mice injected with 1-Scr does not show obvious change (106.3%of GAPDH),compared with that in tumors on mice untreated (p 50.08).(e)Immunofluorescence staining images of tumors on mice untreated (Control),injected with 1or 1-Scr .Furin is stained red and nucleuses are stained blue with DAPI.Scale bar:20m m.products of1upon furin cleavage are1-D s,we also synthesized1-D for in vitro study.In vitro relaxivity measurement results indicated that both1and 1-Scr have relaxivities higher than that of Magnevist.This probably dues to that the molecular weight of1or1-Scr(1645Da)is higher than that of Magnevist(662Da).Interestingly,although1-D has a molecular weight(1860Da)close to that of1,its r1is2-fold more higher than that of1,near2-fold of that of1-Scr and near3-fold of that of Magnevist.This might be ascribed to that the hydrophobic macrocyclic ring of1-D increases its rotational correlation time(t r) in aqueous solution,suggesting that1is a‘‘smart’’MR contrast agent susceptive to furin.Since2and2-Scr are the europium analogs of1and1-Scr respect-ively,their intracellular behavior should represent that of1or1-Scr accordingly.For2-Scr,it is the diastereoisomer of2.Therefore,it should have similar cell permeability to that of2,proven by the TPLM imaging of2and2-Scr on furin-deficient LoVo cells (Supplementary Fig.S19).The difference between the two TPLM images(i.e.,Fig.5e&f)suggests that2could be intracellularly cleaved by furin and condense at the sites of furin while2-Scr could not be trapped inside the cells because2-Scr is not susceptible to furin.To our best of knowledge,caspases and cathepsins are also able to hydrolyze a peptide substrate to yield a N-terminal cysteine motif. However,they have their own specific substrates for cleavage instead of RVRR(e.g.,DEVD for caspase-3and ZVKM for cathepsin B)29,30. Therefore,the specificity of1(or2)to furin for condensation should be much higher than those to other proteases.Interestingly,the intracellular Gd-NPs observed inside the cells after incubation with 1are much smaller than those obtained via in vitro incubation of1 with furin(24.0nm vs.57.1nm).We suspected that this might due to high viscosity of cytosol and the intracellular fibrous networks of the cells hindering the small Gd-NPs from further aggregation. Preliminary results of in vivo imaging MDA-MB-468tumors with 1were obtained.MRI results indicate that1is obviously better than 1-Scr for MDA-MB-468tumor imaging even in the mice with lower expression of furin protein,which further suggests that1is a power-ful probe.The big difference of Gd contents in the organs(lung,liver, spleen,and kidney)except brain between the mice treated with1and 1-Scr at240min(Supplementary Table S1)might be ascribed to the structural difference between1and1-Scr.Detailedly,cleavage of the amide bond between the Cys and Arg motifs of1by the proteinase (furin or other proteinases)in these organs results in condensation reaction and formation of the Gd-NPs which trap the agent in the tissues/organs.In contrast,even the amide bond between the Cys and Arg motifs of1-Scr is cleaved by the proteinase resulting in the condensation and formation of nanoparticles,the Gd-DOTA motif of1-Scr is excluded from neither the condensation reaction nor the nanoparticle formation thereafter.Thus,it is conceivable that the Gd-DOTA motif cleaved from1-Scr should have a smaller molecular weight and be excreted from the body within a very short time window(the plasma half-life for Gd-DOTA is90min in patient with normal renal function).HE staining results indicate that the MR CAs designed in our work are biocompatible,suggesting that1could be likely developed for clinical trial in the near future.In summary,taking advantage of a biocompatible condensation, we have successfully developed the second generation of new smart Gd-based MR contrast agent(i.e.,1)for imaging in vitro and in vivo. 1is susceptive to furin,a protease overexpressed in tumor.Upon furin cleavage,1condenses to form amphiphilic dimer(1-D)and the latter self-assembles into Gd-NPs thereafter.Relaxivity of1-D is more than2-fold of that ing the europium analog of1(i.e., 2),we directly imaged the intracellular condensation of2in furin-overexpressed MDA-MB-468cells.By incubating the cells with1for 8h,for the first time to our best of knowledge,we uncovered and characterized the intracellular Gd-NPs self-assembled from the condensation products of this small molecule uptaken by the pared with that of its scrambled control probe1-Scr,1 showed enhanced MR contrast within MDA-MB-468tumors. Immunofluorescence staining of the tumors indicated that it is furin to trap1in tumors.Encouraged by these exciting results above, we envisioned that more‘‘smart’’probes based on other proteases overexpressed in tumors could also be invented for tumor imaging, using this versatile condensation platform or other‘‘click chemistry’’techniques31.MethodsGeneral methods.All the starting materials were obtained from Adamas or Sangon mercially available reagents were used without further purification, unless noted otherwise.All other chemicals were reagent grade or better.Furin was purchased from Biolabs(2,000UmL21);one unit(U)is defined as the amount of furin that releases1pmol of methylcoumarinamide(MCA)from the fluorogenic peptide BOC-RVRR-AMC(Bachem)in one minute at30u C.1H NMR spectra were obtained on a300MHz Bruker AV300.MALDI-TOF/TOF mass spectra were obtained on a time-of-flight Ultrflex II mass spectrometer(Bruker Daltonics),HPLC analyses were performed on an Agilent1200HPLC system equipped with a G1322A pump and in-line diode array UV detector using a YMC-Pack ODS-AM column with CH3OH (0.1%of TFA)and water(0.1%of TFA)as the eluent.SEM images were obtained on JEOL-JSM-6700F electron microscope at an accelerating voltage of5.0KV.TEM images were obtained on a JEOL2010electron microscope,operating at100KV.The cryo-dried samples were prepared as following:a copper grid coated with carbon was dipped into the suspension solvent and placed into a vial,which was plunged into liquid nitrogen until no bubbles were apparent.Then water was removed from the frozen specimen by a freeze-drier.ICP-AES measurements were conducted on an ICP-96B machine equipped with a PGS-2atomic emission spectrometer(Zeiss).ICP-MS measurements were conducted on an X Series2machine(Thermo Fisher Scientific).Cell culture.MDA-MB-468human breast adenocarcinoma epithelial cells and Human colon carcinoma LoVo cells were cultured in Dulbecco’s modified eagle medium(GIBCO)supplemented with10%fetal bovine serum(FBS,GIBCO). Two photon laser microscopy.MDA-MB-468or LoVo cells were cultured on the glass slide,incubated with2or2-scr at100m M for8h,washed with phosphate buffered saline(PBS)for three times,fixed with4%paraformaldehyde at RT for 30min,washed with PBS a further three times and once with distilled water.Then the cells were mounted with50%glycerol and imaged under a Zeiss710confocal laser-scanning microscope equipped with a Coherent Mrux1titanium:sapphire mode-locked laser.The excitation wavelength for TPLM was725nm(23362.5nm5 725nm).A565–636nm band pass filter was used for cell imaging.Electron microscopic imaging.MDA-MB-468cells were incubated with1or1-scr at 100m M for8h,washed for three times with phosphate-buffered saline(PBS),fixed with2.5%glutaraldehyde at RT for30min.The cells were then detached from culture dishes,centrifuged(300rpm,15min)and washed with PBS for a further three times, and then stained with1%OsO4in double-distilled water for1.5h.Then the cells were dehydrated in ethanol and embedded in Epon.Thin sections(80nm)were cut and mounted on copper grids,stained with saturated solution of uranyl acetate and lead citrate for electron microscope observation.In vitro and in vivo MRI.The in vitro phantom MR experiments were performed on a1.5T(Simens,Magnetom-essenza)and3T(Simens,Trio-Tim)scanners,using a head RF coil.The scanning procedure began with a localizer and then consisted of a series of inversion-prepared fast spin echo images,identical in all aspects(TR 1740ms,TE13,BW140kHz,percent phase field of view50,slice thickness3mm, matrix1363136,NEX1)except for the inversion time(TI)which was varied as follows:1500,1200,1000,800,500,400,200,150,100,and75ms.Signal intensity(SI) versus TI relationships were fit to the following exponential T1decay model by non-linear least squares regression:SI(TI)5A1*exp(2TI/T1)1SI(0).Relaxation rates (R1)were determined as1/T1.Longitudinal molar relaxivities(r1,units of s21mM21) were calculated as the slope of R1vs[CA]after the determination of true Gd concentration of each sample by the ICP-AES or ICP-MS measurement.The in vivo MR imaging of MDA-MB-468tumor xenografted nude mice was performed on3T scanner(Simens,Trio Tim),using head RF coil.Female mice of3–4weeks old were provided by Sun Yat-sen University Laboratory Animal Center(Guangzhou,China). MDA-MB-468tumor lesions were established by subcutaneous dorsal flank injection of43107tumor cells in100m L PBS for each mouse.Visible tumors were normally observed2–4weeks after injection.The tumor-xenografted mice were then subjected randomly into two groups for tail vein injections of1or1-scr(1st injection:0.15mmol/kg at0min;2nd injection:0.15mmol/kg at50min).The images were taken at a time sequence from0min to240min using T1-weighted MR acquisition sequence with the following parameters:TR2000ms,TE70,BW289kHz,percent phase field of view60,slice thickness2mm,matrix1443144,NEX1.The intensity of MR signal in tumor for each test was determined by standard region-of-interest measurement with ImageJ.。

超微超顺磁性氧化铁纳米粒及其在肿瘤磁共振成像中的应用

超微超顺磁性氧化铁纳米粒及其在肿瘤磁共振成像中的应用

超微超顺磁性氧化铁纳米粒及其在肿瘤磁共振成像中的应用刘国华【摘要】超微超顺磁性氧化铁纳米粒是一种新型的磁共振对比剂,具有血浆半衰期长及易被巨噬细胞吞噬摄取等特点,在磁共振血管成像、肝脏骨髓肿瘤的鉴别、淋巴结的良恶性鉴别、肿瘤病灶的显示及肿瘤免疫成像等方面有着良好的应用前景.随着在基础及临床方面研究的深入,其必将使现有的一些肿瘤磁共振成像模式发生深刻的变革.【期刊名称】《医学综述》【年(卷),期】2010(016)016【总页数】4页(P2494-2497)【关键词】超微超顺磁性氧化铁纳米粒;对比剂;磁共振成像【作者】刘国华【作者单位】南京医科大学附属苏州市立医院东区呼吸科,江苏,苏州,215001【正文语种】中文【中图分类】R445.2恶性肿瘤严重危害着人类健康，近年来纳米生物技术的发展为肿瘤的早期诊治提供了新的机遇，其中超微超顺磁性氧化铁纳米粒(ultrasmall superamagmetic iron oxide，USPIO)具有粒径小，血浆半衰期长，易集中分布在网状内皮细胞丰富的组织和器官等特点，有助于提高该部位肿瘤与正常组织的磁共振成像(magneticresonance imaging，MRI)对比度。

已有大量研究证实，其在磁共振肿瘤血管成像、组织灌注、网状内皮系统肿瘤成像方面有着良好的应用前景。

此外，其易于在细胞间通透移动，适用于带特定抗原的肿瘤细胞免疫显像。

目前，国内在这方面的研究尚处于初始阶段。

现就其在肿瘤MRI方面的应用研究作一综述。

1 USPIO的理化性质及磁共振增强原理USPIO是由不同的外层材料(主要是葡聚糖)包裹Fe2O3或Fe3O4形成的氧化铁纳米粒，目前，多种USPIO制剂尚处于试验阶段，但也有数种制剂如AMI-227、NC100150、ferumoxytol等已应用于人体。

USPIO体积一般＜50 nm，比普通的超顺磁性氧化铁颗粒更小，且表面包有较厚的葡聚糖层，因此，与血浆蛋白和调理素的作用减弱，影响了吞噬细胞对其的摄入，血循环半衰期长达100 min以上，可用来作为血池显像剂，同时，长循环时间也使得其除了被肝脾单核吞噬细胞系统摄取外，尚可以通过毛细血管壁，从而更广泛地分布于深部组织的巨噬细胞内(如淋巴结、骨髓、肺、脑、肾等组织)，使得巨噬细胞系统成像成为可能［1］。

磁珠羧基活化原理探究

磁珠羧基活化原理探究

磁珠羧基活化原理探究文章标题：磁珠羧基活化原理探究引言：磁珠羧基活化是一种广泛应用于生物化学、药物研发和分子生物学领域的方法。

通过磁珠表面修饰羧基，可以增强其对生物分子的亲和性，从而实现对目标分子的高效分离和纯化。

本文将深入探究磁珠羧基活化的原理，包括其基本原理、相关技术和应用前景，旨在帮助读者更全面、深刻地理解这一技术。

一、磁珠羧基活化的基本原理磁珠羧基活化是通过在磁珠表面引入羧基实现的。

羧基的引入可以通过多种方法实现，例如在磁珠表面修饰羧基官能化试剂，或通过微生物发酵产生羧基化合物。

羧基具有较高的亲和性，可以与多种生物分子发生靶向相互作用，从而实现分离和纯化的目的。

二、磁珠羧基活化的相关技术1. 羧基化试剂的选择与合成在实施磁珠羧基活化之前，需要选择合适的羧基化试剂，并进行合成。

常见的羧基化试剂包括羧酸、酐、酯等，其选择应根据目标分子的特性、磁珠的表面性质以及实验条件等进行综合考虑。

2. 磁珠表面的羧基修饰一旦合成好羧基化试剂，就可以将其与磁珠进行反应，实现磁珠表面的羧基修饰。

修饰过程中需要注意反应条件的控制，以确保反应的效果和磁珠的稳定性。

3. 磁珠羧基的功能化与固定化磁珠经过羧基修饰后，可以进一步进行功能化和固定化。

功能化可以通过引入特定的官能基实现，从而增强对目标分子的亲和性。

固定化可以通过交联剂或辅助支撑物实现，以提高磁珠的稳定性和机械强度。

三、磁珠羧基活化的应用前景磁珠羧基活化在生物化学、药物研发和分子生物学等领域具有广阔的应用前景。

其主要应用包括：1. 生物分子纯化磁珠羧基活化可以实现对蛋白质、核酸和多肽等生物分子的高效分离和纯化。

通过调节羧基的结构和密度，可以实现对目标分子的选择性捕获，从而提高分离的纯度和产量。

2. 药物靶标筛选磁珠羧基活化可以用于药物靶标的筛选和鉴定。

通过将药物样品与具有特定亲和性的磁珠结合，可以实现对药物靶标的直接捕获和分离，从而评估药物的活性和选择性。

3. 分子诊断与检测磁珠羧基活化在分子诊断与检测中也具有广泛应用。

纳米医学在血栓形成中的应用

纳米医学在血栓形成中的应用

纳米医学在血栓形成中的应用王欣【摘要】Nanomedicine is an emerging subdiscipline applying nanotechnology in the field of medicine. N anomaterials are widely used in diagnosis and therapeutic areas such as medical imaging and targeted drug delivery. In recent years, along with continuous research and development of nanotechnology and the emergence of new nano-materials represented by superparamagnetic iron oxide, nanomedicine application in the diagnosis and treatment of cardiovascular disease and stroke has seen some progress. Here is to make a review' on the application of nanomedicine in the imaging and treatment of thrombosis.%纳米医学是纳米技术应用于医学领域中的一门新兴分支学科,纳米材料广泛应用于医学影像、药物靶向传递等疾病的诊断治疗领域.近年来,随着纳米技术的不断研发,以超顺磁性氧化铁为代表的新型纳米材料的出现,使纳米医学应用于脑卒中及心血管疾病的诊治有了一定进展.现就纳米医学在血栓形成的影像及治疗方面的应用予以综述.【期刊名称】《医学综述》【年(卷),期】2012(018)021【总页数】3页(P3602-3604)【关键词】纳米医学;血栓形成;影像学;治疗【作者】王欣【作者单位】哈尔滨医科大学附属第一医院神经内科,哈尔滨,150001【正文语种】中文【中图分类】R741纳米技术是20世纪90年代出现的一门新兴技术，将纳米技术应用于临床医学将为疾病的诊治带来革命性的突破。

磁共振成像原理教学课件

磁共振成像原理教学课件
M z M0 (1 et /T1 )
一般说来，纵向弛豫时间远大于横向弛豫时间。而且，不 同的组织与器官的弛豫时间显著不同，从而对软组织及器 官有特殊的分辨能力。在主磁场为0.4~2T时，人体组织 T1~103ms，T2~102ms。
纵向弛豫与纵向弛豫时间常数的关系 t=T1时, Mz/M0=1-e-1=63%
与FID同相位的SE(Hahn回波）
与FID反相的SE(CPMG回波）
回波时间TE
自旋回波信号幅度随相位重聚达到峰 值的时间。
回波时间信号的变化
180°翻转脉冲只能使由于静磁场不 均匀所造成的自旋去相位产生相位重 聚
自旋回波信号的变化
四、弛豫时间的测量（自旋回波（SE)法）
在磁共振现象中， 物质的宏观磁化 强度及变化与自 旋核的密度、 T1、T2密切相关， 但这些信息不能 直接测出，只能 通过弛豫过程中 辐射的射频信号 来分析。
方向—自旋轴
自旋磁矩
原子核自旋运动I产生的微观磁场
—磁旋比，磁矩与角动量之比
—约化普朗克常数
1.05457261034 J s
净自旋 • 只有奇数质子或奇数中子数的原
子核产生的自旋磁矩 • 泡利不相容原理：
原子核内成对质子或中子的自旋 相互抵消
第一节：磁共振现象
一、旋进 （precession)：角动量受到一个与之垂直 的力矩的作用，角动量矢量沿一圆周转动的现象。
M=·B0·N/T
—常数 B0—磁场强度 N—单位体积样体质子数（组织质子密度） T—绝对温度
核磁矩在净磁场0作用下 产生力矩
= 0
核磁矩对时间d的 变化 率
B
dt
• 核磁矩在净磁场0中的运动
• 磁矩分解为Z轴、X-Y平面矢量 • 旋进过程中Z轴矢量方向不变 • X-Y平面矢量绕Z轴方向不断变化 • X-Y平面矢量相位随机 • 不形成宏观磁化矢量
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3. Surface coatings and functionalization
3.1. Polymeric coatings
• “one-pot”synthesis methods
• 一步合成法相对于多步表面修饰的优势是：减少纳米颗粒聚集； 减少处理程序。但是在纳米晶体成核的过程中加入聚合物对晶体 的结构和MNP的形态有明显的影响。 • Lee et al.[83][84][85]
3. Surface coatings and functionalization
Polymeric coatings
Functional ligands
Surface coatings and functionalization
Liposomes and micelles
Core–shell structures
3. Surface coatings and functionalization
3.1. Polymeric coatings
• • • • • MNP包被聚合物举例： 1.多糖右旋糖苷 Weissleder and co-workers:MION[42],CLIO[68]. 2.PEG PEG可以用来减少巨噬细胞对纳米颗粒的摄入，并延长纳米颗粒在体 内的血液循环时间，连接PEG到MNP表面的方法有： • 在氧化物表面接枝；MNP表面的聚合作用;溶胶-凝胶法修饰。 • Kohler et al. bifunctional PEG silanes[18,19,76,77] • Lee et al. a protein resistant poly(TMSMA-rPEGMA) copolymer comprised of silane anchoring groups and PEGbranches[78]
Magnetic nanoparticles in MR imaging and drug delivery
李凯 D201577434
• 1. Introduction • 2. Magnetic nanoparticles . • 3. Surface coatings and functionalization • 4. Pharmacokinetics and biodistribution • 5. MR imaging • 6. Drug delivery • 7. Conclusions
2. Magnetic nanoparticles
2.2. Iron oxide nanoparticles
• 提高磁性的应用：分子显像
• [44] J.H. Lee, Y.M. Huh, Y.W. Jun, J.W. Seo, J.T. Jang, H.T. Song, S. Kim, E.J. Cho, H.G. Yoon,J.S. Suh, J. Cheon, Artificially engineered magnetic nanoparticles for ultrasensitive molecular imaging, Natural Medicines 13 (2007) 95–99. • [46] G. Baldi, D. Bonacchi, M.C. Franchini, D. Gentili, G. Lorenzi, A. Ricci, C. Ravagli,Synthesis and coating of cobalt ferrite nanoparticles: afirst step toward the obtainment of new magnetic nanocarriers, Langmuir 23 (2007) 4026–4028. • [47] S. Rana, A. Gallo, R.S. Srivastava, R.D.K. Misra, On the suitability of nanocrystalline ferrites as a magnetic carrier for drug delivery: functionalization, conjugation and drug release kinetics, Acta Biomaterialia 3 (2007) 233–242.
2. Magnetic nanoparticles
2.3. Metallic nanoparticles
• 金属磁性纳米颗粒主要由铁，钴，镍组成，缺点是化学性质不稳 定，容易在水和氧气存在时形成氧化物。常用的保护手段是形成 核-壳结构。
• [48] D.L. Huber, Synthesis, properties, and applications of iron nanoparticles, Small 1(2005) 482–501. • [49] S. Peng, C. Wang, J. Xie, S. Sun, Synthesis and stabilization of monodisperse Fe nanoparticles, Journal of the American Chemical Society 128 (2006) 10676–10677. • [50] Y. Qiang, J. Antony, A. Sharma, J. Nutting, D. Sikes, D. Meyer, Iron/iron oxide core–shell nanoclusters for biomedical applications, Journal of Nanoparticle Research 8(2006) 489–496.
3. Surface coatings and functionalization
3.4. Functional ligands
MNP上连接的配体有： 靶向试剂； 渗透促进剂； 光
3. Surface coatings and functionalization
2.1. Magnetic properties
• 定义材料在磁场作用下，磁化强度M与磁场强度H的比值为磁化率： χ=M/H • 对于抗磁性物质，磁矩(m=iSn)对磁场强度反向平行，磁化率为 (-10-6到-10-3 ) • 对于超顺磁性物质，磁矩对磁场强度正向平行，磁化率为(10-6到10-3 ) • 超顺磁性（sup：如果磁性材料是一单畴颗粒的集合体，对于每一个颗粒而言，由于磁性原子或离子 之间的交换作用很强，磁矩之间将平行取向，而且磁矩取向在由磁晶各向异性所决定的易磁化方向上， 但是颗粒之间由于易磁化方向不同，磁矩的取向也就不同。现今，如果进一步减小颗粒的尺寸即体积， 因为总的磁晶各向异性能正比于K1V，热扰动能正比于kT（K1是磁晶各向异性常数，V是颗粒体积，k 是玻尔兹曼常数，T是样品的绝对温度），颗粒体积减小到某一数值时，热扰动能将与总的磁晶各向 异性能相当，这样，颗粒内的磁矩方向就可能随着时间的推移，整体保持平行地在一个易磁化方向和 另一个易磁化方向之间反复变化。从单畴颗粒集合体看，不同颗粒的磁矩取向每时每刻都在变换方向， 这种磁性的特点和正常顺磁性的情况很相似，但是也不尽相同。因为在正常顺磁体中，每个原子或离 子的磁矩只有几个玻尔磁子，但是对于直径5nm的特定球形颗粒集合体而言，每个颗粒可能包含了 5000个以上的原子，颗粒的总磁矩有可能大于10000个玻尔磁子。所以把单畴颗粒集合体的这种磁性 称为超顺磁性。
3. Surface coatings and functionalization
3.2. Liposomes and micelles
• 脂质体作为药物载体的优势是它们在体内的行为已经被确认，比 如PEG化导致较长的血液循环时间，与此同时PEG还能包埋大量的 MNP核并将它们传送到靶位，同时还能避免MNP的稀释。耦连治 疗剂增强了这些传递工具的多功能性。 • 多功能胶束耦连两亲嵌段共聚物也有类似的应用。 • Martina et al.[89]磁流体负载脂质体（MFLs）。
2.2. Iron oxide nanoparticles
磁性纳米颗粒合成方法： 1.湿化学方法：狭义，共沉淀法；广义，有液相参加的、通过化学 反应来制备材料的方法统称为湿化学法，如化学液相沉积（CBD）、 电化学沉积（电镀）、溶胶凝胶等； 2.激光热解法（laser pyrolysis）； 3.气相沉积法（vapor deposition）； 4.高温合成法（high-temperature decomposition）（Sun et al.
2. Magnetic nanoparticles
2.2. Iron oxide nanoparticles
• 胶体铁氧化物纳米颗粒（SPIO and USPIO）多应用在生物医药中： • 生物相容性； • 生物可降解性； • 磁性； • 容易合成。
2. Magnetic nanoparticles
2. Magnetic nanoparticles
2.4. Bimetallic nanoparticles
• 双金属纳米颗粒 • 铁铂合金: • 跟单一成分的金属纳米颗粒相比，合金纳米颗粒的化学稳定性更 好，而且这些磁性纳米颗粒的表面可以连接氨基或羧基类表面活 性剂，可以提高他们在水溶液中的溶解性。 • Hong et al.[52];Sun et al.[53]; Gao et al. [54,55];[56];[57]. • 铁钴合金: • Bai and Wang[59]; Seo et al.[60].
3. Surface coatings and functionalization
3.3. Core–shell structures
• 核-壳结构的壳可以能够保护磁性核心防止化学降解，阻止可能的 化学毒性物质的释放。用于MRI显影剂和药物传递载体。 • 保护层材料： • SiO2：水相条件下稳定，合成方便；Ma et al.[93] • 金:化学性质稳定，易在自己表面通过烷硫醇形成自组装单层膜 （SAMs），同时化学惰性也导致很难在MNP表面形成金壳。 • 最新合成方法有：反向微乳液法；综合湿化学法；激光辐射法。 • MNP异质二聚体（Fig.1E）
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