纳/微米材料及器件的生物医学应用虚拟专辑代表性论文8：利用多层细胞培养模型揭示纳米颗粒在实体肿瘤中的吸收和分布
【引言】
摘要
纳米颗粒在离开肿瘤血管进入肿瘤微环境后的行为仍缺乏实验研究。Michael’s Hospital的Devika Chithrani等人利用多细胞层模型研究了金纳米颗粒在组织类型结构内的吸收和分布动力学。结果表面，纳米颗粒的吸收和传输依赖于肿瘤细胞的类型：与MCF-7细胞相比，金纳米颗粒在MDA-MB-231细胞内的穿透距离更深。利用CytoViva成像法对金纳米颗粒在细胞内、外的分布进行了成像分析。多细胞层模型能有效地实现对肿瘤组织的模拟，使其成为实体肿瘤中颗粒分布功效评估的有力工具。
撰写的综述发表于Nano-Micro Letters上2015年第7卷第2期.
全文链接：
文章引用信息：
Darren Yohan • Charmainne Cruje • Xiaofeng Lu • Devika Chithrani,Elucidating the Uptake and Distribution of Nanoparticles in Solid Tumors via a Multilayered Cell Culture Model,Nano-Micro Lett.(2015) 7(2):127–137, http://dx.doi:10.1007/s40820-014-0025-1
【图文导读】
Fig. 1 Use of MCL cell model to understand the NP transport through the tumor tissue. a Transport of GNPs through the blood vessels and enters tumor vasculature. The interface between tumor vasculature and tumor tissue is highlighted with(a) yellow box. (b) GNPs escape the tumor vasculature through leaky endothelial cells (1) and enter tumor cells through ECM. (c) Description shown in B is modeled using proposed MCL cell model. MCL act as a tumor tissue being fed by tissue culture media containing GNPs (2). (Color figure online)
Fig. 2 Growth of MCLs. (a) Diagrammatic representation of the apparatus used to culture MCLs. Tissue culture inserts are held suspended in stirred media (top left). The set-up was placed in a humidified incubator with 5 % O2, 5 % CO2, and 95 % N2. After the growth, GNPs were introduced into the media to investigate the NP transport through tissue (top right). (b) A cross-section of an unstained MCF-7 tissue. (c) A cross-section of a MCF-7 tissue stained with eosin to map the ECM. Areas marked in green belong to ECM, while the unstained regions represent cells. (Color figure online)
Fig. 3 Visualization and mapping of GNPs in cells using CytoViva HSI optical microscopy. (a) The unmapped dark-field HSI image with GNPs visible as bright spots. (b) The result of a spectral angle mapping on the HSI image. GNPs have been labeled red as a result of matching spectra from individual pixels. (c) GNP spectra from few NP clusters localized within cells and the reference spectra (inset) used to create the spectral angle map in (b). (Color figure online)
Fig. 4 Characterization of monolayer and multilayer cell structures. (a)–(b) Comparison of growth curves for the MDA-MB-231 and MCF-7 cell lines at monolayer and multilayer level, respectively.( c)–(d) A monolayer and multilayer cross-section of MDA-MB-231 cells stained with eosin to highlight the ECM, respectively. Cell population doubling times for MCF-7 and MDA-MB-231 monolayer cell cultures were 38.83 and 37.10 h, respectively. Cell population doubling times for MCF-7 and MDA-MB-231 multilayer cell cultures were 48.36 and 51.07 h, respectively. Error bars represent the standard deviation and n = 3. There was no statistically significant difference via one-way ANOVA test between the monolayer and multilayer groups (p = 0.6907 for MCF-7 and p = 0.3751 for MDA-MB-231)
Fig. 5 GNP uptake in monolayer cell models. (a) NP uptake per cell as a function of cell density. (b) Total uptake of NPs as a function of cell density. (c)–(d) Samples of H&E stained monolayer MDA-MB-231 and MCF-7 cells with GNPs present mostly in the cells. Error bars represent the standard deviation and n = 3. One-way ANOVA test over the cell densities for each cell line revealed that there was no significant difference in NP uptake for the MDA cell line (p = 0.565) and for the MCF-7 cell line (p = 0.3541)
Fig. 6 Differences in extracellular matrix (ECM) in MDA-MB-231 and MCF-7 tissue structures. (a)–(c), MCL tissue of MCF-7 cells at 910 and 960 magnification, respectively. (b)–(d), MCL tissue of MDA-MB-231 cells at 910 and 960, respectively. Differences in the ECM structure can be seen at both magnifications. MCF-7 tissue had a much more organized ECM structure, while MDA-MB-231 tissue has a disorganized ECM structure which allowed easy penetration of molecules into deeper tissues
Fig. 7 GNP uptake in multilayer cell models.( a) Accumulation of GNPs in tissue as a function of its thickness. NPs were able to penetrate deep into tissue in MDA-MB-231 tissue due to the breakdown in ECM matrix. In MCF-7 tissue, most NPs were localized at the top layers and properly organized ECM acted as a barrier for their transport deep into the tissue. (b) The normalized percent increase in GNP uptake as a function of tissue thickness. Error bars represent the standard deviation and n = 3
Fig. 8 Mapping of NP transport through different layers of a thicker tissue.(a) A schematic depicting the multiple layers of a tissue cross-section. (b) Accumulation of NPs in different layers of tissue. (c)–(d) Mapping of the NP distribution in MDA-MB-231 and MCF-7 tissue (with GNPs labeled in red), respectively. (e)–(f) A sample of reflectance spectra of GNPs localized in ECM and cells, respectively. Error bars represent the standard deviation and n = 3. (Color figure online)
虚拟专辑（二）纳/微米材料及器件的生物医学应用
本期虚拟专辑主要介绍纳米材料及器件在生物医学领域的研究，选自近两年发表在Nano-Micro Letters上的9篇代表性论文，敬请阅读并复制链接打开下载（免费），并欢迎投稿。
⊙ 1. 综述：微流体在乳腺癌诊断方面的应用
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⊙ 2. 综述：电化学纳米医学传感器在生物医学领域的应用展望
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⊙ 3. 综述：ZnO纳米颗粒的抗菌活性和毒性机制
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⊙ 4. 金纳米颗粒单层和多层细胞模型在纳米-微界面上相互作用的尺寸依赖性
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⊙ 5. 具有高抗菌抗癌特性的碳纳米管内嵌植物化学官能化Cu/Ag纳米颗粒复合物
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⊙ 6. 牛血清白蛋白耦联磁性Fe3O4 纳米颗粒提高生物相容性与磁热疗性能
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⊙ 7. 细胞在阳极氧化的多尺寸二氧化钛纳米管阵列表面的行为研究
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⊙ 8.利用多层细胞培养模型揭示纳米颗粒在实体肿瘤中的吸收和分布
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⊙ 9. 阳离子多赖氨酸修饰磁性氧化铁纳米粒颗粒用于肺癌细胞高效标记
链接10.1007/s40820-015-0053-5
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