肿瘤芯片的研究进展及方向

17
图b的 示意 结构
2020/8/11
A droplet of fibrin loaded with green fluorescent protein (GFP)–A549 lung cancer cells was printed between
linear arrays of chemoattractant capsules (right) and
2020/8/11
Jihoon Ko. Lab on a Chip, 2019.
20
2020/8/11
Yi H G. Nature Biomedical Engineering, 2019.
缺氧 细胞 增殖 细胞
细胞 迁移
21
乳腺 癌骨 转移 模型
2020/8/11
比例
速度
成肌 细胞
Jessie S. Jeon et al. PNAS, 2014.
紫杉醇处理
2020/8/11
Tumor-on-a-chip platform to investigate progression and drug
12
静态 培养
三 角 形 小 柱 结 构
2020/8/11 Jordan A. Whisler, TISSUE ENGINEERING: Part C, 2014.
距离
动态 和静 态转 移情 况
22
黑色素瘤
成纤维细胞
共培养和缺氧 促进肿瘤细胞
的迁移
2020/8/11
Su-Yeong Jeong. Plos One, 2016.
23
结直肠癌与成纤维细胞的相互作用
结直肠癌
成纤维细胞
共培养促进肿瘤细胞成球率
2020/8/11
Su-Yeong Jeong. Plos One, 2016.
4. My question and thinking
1. Background CONTENTS
2. The application of tumor on a chip
3. Opportunities and challenges in the future
4. My question and thinking
blank control capsules (left)
Meng F,. Advanced Materials, 2019.
M4A4:黑色素瘤细胞 HUVEC:人脐静脉内
皮细胞
18
Metastatic tumor model
肿瘤转移过程及收集
Intravasation and spread (days 9 and 12) Scale bar: 500
24
2020/8/11
Su-Yeong Jeong. Plos One, 2016.
肿瘤细胞招募 成纤维细胞
25
Tumor-on-a chip (nanomedicine)
介孔二氧 化硅（90 nm）的细 胞摄取
Cell uptake
2020/8/11
瞬时给药与连 续灌注对细胞 摄取的影响， 连续促进细胞
13ห้องสมุดไป่ตู้
可以形成直径约为10微米 的血管网络，且网络直径
相互贯通
2020/8/11 Jordan A. Whisler, TISSUE ENGINEERING: Part C, 2014.
14
血管的形成 及单核细胞
灌注
2020/8/11
不同形式单核 细胞灌注对于 肿瘤细胞外渗
的影响
A. Boussommier-Calleja, Biomaterials, 2019.
µm
2020/8/11
Meng F,. Advanced Materials, 2019.
19
Tumor-on-a chip (tumor metastasis or cells interactions)
微流体 结构设 计图
肿瘤在 不同因 子处理 条件转 移和侵 染情况
抗肿瘤 血管生 成药物 筛选
Siming Lu et al, Lab on a Chip, 2018
9
多器官抗癌药 物毒性评价
3D生 物打 印的 模型
2020/8/11
Aleksander Skardal, Scientific Reports, 2017.
10
2020/8/11
Tree-organoid
platform:
Viability of lung, liver, and
cardiac constructs under (a) a no
drug control condition or (b)
bleomycin afer maintenance in a
3-organoid platform for 9 days.
cells; Red – Ethidium
homodimer-stained
dead
cells.(c–e) Cardiac organoid
beating plots on day 9.
Aleksander Skardal, Scientific Reports, 2017.
11
Tumor-on-a chip (microvasculature) 乳腺癌血管化模型
15
内皮细胞+患者的胶质瘤细胞，共培养在微流体芯片
2020/8/11
通 透 性 评 价
Yang Xiao. Advanced Science, 2019.
16
两种不同细胞在血管上的定位情况
肿瘤细胞微血管上的定位
2020/8/11
Yang Xiao. Advanced Science, 2019.
Tumor-on-chips are micro-engineered biomimetic systems that represent key functional units of living tumor.
2020/8/11
Jungho Ahn, et.al, Bioemgineering, 2017.
4
Navid Kashaninejad, et.al, Micromavhines, 2016.
1. Background CONTENTS
2. The application of tumor on a chip
3. Opportunities and challenges in the future
Background of Tumor on a chip
Definition
Microfluidics, which is a study of fluid flow in micron-size domains, proves to be an effective technology in cancer study both in vivo and in vitro.
29
冲洗
转铁蛋白改性后
研究改性前后对于纳米颗粒累积量和穿透深度的影响，同时评 价流速的影响（改性和高流速提高累积和穿透深度）
2020/8/11
Alexandre Albanese, et al, Nature communications, 2013.
30
动物实验验证体外肿 瘤芯片的结果可行性 （主要验证颗粒尺寸）
2020/8/11
Nandini Dhiman, Biosensors and Bioelectronics, 2019.
7
单通道动态 药物灌注
2020/8/11
Siming Lu et al, Lab on a Chip, 2018
8
效果显著
评价乙酰胺酚和索拉菲尼两种药物的毒性评价
2020/8/11
Recent Advances of Tumor on a Chip
Reporter : Date: 2 Oct, 2018
2020/8/11
1
1. Background CONTENTS
2. The application of tumor on a chip
3. Opportunities and challenges in the future
M. R. Carvalho , Science Advances, 2019.
33
原卟啉
活性氧
Ratio：1:1
5-ALA：氨基酮戊酸(胞内转化)
2020/8/11
Yamin Yang et al, Lab on a Chip, 2015
34
2020/8/11
金纳米颗粒提高细胞摄取
The specific objectives of this investigation were to 1) develop a microfluidic-based in vitro 3D breast cancer tissue model that can mimic the heterogeneous cancer microenvironment and emulate physiologic conditions, 2) evaluate breast cancer tissues for PDT efficacy by dynamically injecting therapeutic agents (i.e. PS and Au NPs) and studying their distribution profiles, and 3) investigate the effects of light penetration on PDT by providing a suitable depth of cancer tissue
Bleomycin was added on day 3.
Little cell death was observed,
however, cardiac organoids in
the bleomycin group appeared
somewhat disaggregated. Green
– Calcein AM-stained viable
摄取
Jialang Zhuang et al, Advanced Science, 2019.
26
不同粒径的介孔二氧化硅的细胞摄取情况， 低粒径促进细胞摄取
2020/8/11
Jialang Zhuang et al, Advanced Science, 2019.
27
三种不同表面处理（透明质酸酶,洛沙坦和法素地尔）对大 尺寸纳米颗粒细胞摄取的影响
Unanticipated side efect
detection in a three organoid
liver, heart, and
lung system – Bleomycin
induces lung infammatory
factor-driven cardiotoxicity. (a,b)
2020/8/11
Alexandre Albanese, et al, Nature communications, 2013.
31
VEGF对于肿瘤血管侵染作用
2020/8/11
M. R. Carvalho , Science Advances, 2019.
32
纳米颗粒扩散
药物毒性评价
2020/8/11
2020/8/11
6
Drug screening
Schematic diagram showing preclinical models for anticancer drug screening and the current research and development areas in the field of ‘tumor-on-chip’ for anticancer drug screening applications.
2020/8/11
Jialang Zhuang et al, Advanced Science, 2019.
28
40 nm
110 nm
Treated 1 h
40,70,110,150 nm Before and after clear
2020/8/11
Alexandre Albanese, et al, Nature communications, 2013.
Yamin Yang et al, Lab on a Chip, 2015
4. My question and thinking
The application of tumor on a chip
Drug screening
Tumor formation and
metastasis
Tumor on a chip
Angiogenesis
Evaluation of nanoparticles