Receptor-mediated transcytosis: a mechanism for active extravascular transport of nanoparticles in solid tumors.
Receptor-mediated transcytosis: a mechanism for active extravascular transport of nanoparticles in solid tumors.
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DOI：
10.1016/j.jconrel.2012.05.014
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发表时间：
2012-08-10
期刊：
影响因子：
--
通讯作者：
Li C
中科院分区：
文献类型：
--
作者：
Lu W;Xiong C;Zhang R;Shi L;Huang M;Zhang G;Song S;Huang Q;Liu GY;Li C
靶向纳米粒子为基础的递送系统已广泛用于开发有效的癌症治疗。然而，靶向配体如何影响纳米颗粒在实体肿瘤中的血管外运输仍不清楚。在这里，我们使用表达黑素皮质素1型受体（MC1R）的B16/F10黑色素瘤细胞表明，靶向配体的性质，即它们是激动剂还是拮抗剂，在纳米颗粒从肿瘤血管外渗到血管外液空间后，指导肿瘤摄取和肿瘤内分布。涂有MC1R激动剂的聚乙二醇化中空金纳米球（HAuNS，直径≈40 nm）通过配体-受体结合被内化，而MC1R拮抗剂偶联的HAuNS仍附着在细胞表面。多层肿瘤细胞模型和透射电镜证实了激动剂偶联HAuNS的跨细胞转运。MC1R激动剂-但不是MC1R拮抗剂共轭的纳米颗粒比非靶向haun表现出更高的肿瘤摄取，并通过受体介导的内吞作用和随后的胞吞作用迅速从肿瘤血管中分散。这些结果证实了一种主动转运机制，可以用来克服纳米颗粒有效递送到实体肿瘤的主要生物障碍之一。
Targeted nanoparticle-based delivery systems have been used extensively to develop effective cancer theranostics. However, how targeting ligands affect extravascular transport of nanoparticles in solid tumors remains unclear. Here, we show, using B16/F10 melanoma cells expressing melanocortin type-1 receptor (MC1R), that the nature of targeting ligands, i.e., whether they are agonists or antagonists, directs tumor uptake and intratumoral distribution after extravasation of nanoparticles from tumor vessels into the extravascular fluid space. Pegylated hollow gold nanospheres (HAuNS, diameter≈40 nm) coated with MC1R agonist are internalized upon ligand-receptor binding, whereas MC1R antagonist-conjugated HAuNS remain attached on the cell surface. Transcellular transport of agonist-conjugated HAuNS was confirmed by a multilayer tumor cell model and by transmission electron microscopy. MC1R agonist- but not MC1R antagonist-conjugated nanoparticles exhibit significantly higher tumor uptake than nontargeted HAuNS and are quickly dispersed from tumor vessels via receptor-mediated endocytosis and subsequent transcytosis. These results confirm an active transport mechanism that can be used to overcome one of the major biological barriers for efficient nanoparticle delivery to solid tumors.
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DOI：
10.1083/jcb.200910104
发表时间：
2010-03-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ruoslahti E;Bhatia SN;Sailor MJ
通讯作者：
Sailor MJ
影响因子：
11.2
作者：
Lu W;Zhang G;Zhang R;Flores LG 2nd;Huang Q;Gelovani JG;Li C
通讯作者：
Li C
DOI：
10.1073/pnas.77.10.5754
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
SAWYER, TK;SANFILIPPO, PJ;HADLEY, ME
通讯作者：
HADLEY, ME
影响因子：
3
作者：
Grieco, Paolo;Cai, Minying;Hruby, Victor J.
通讯作者：
Hruby, Victor J.
影响因子：
7.3
作者：
Thirumoorthy, R;Holder, JR;Haskell-Luevano, C
通讯作者：
Haskell-Luevano, C