Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement of tumor penetration through receptor mediated transcytosis in 3D tumor models.
Development of drug loaded nanoparticles for tumor targeting. Part 2: Enhancement of tumor penetration through receptor mediated transcytosis in 3D tumor models.
复制标题
DOI：
10.1039/c3nr90022c
复制
发表时间：
2013-05-07
期刊：
影响因子：
6.7
通讯作者：
Huang X
中科院分区：
文献类型：
--
作者：
El-Dakdouki MH;Puré E;Huang X
我们报告说，受体介导的转胞吞作用可用于促进载药纳米颗粒（NP）穿透肿瘤。我们合成了含有高荧光核心的透明质酸 (HA) 涂层二氧化硅纳米颗粒 (SNP)，可靶向癌细胞表面表达的 CD44。尽管之前的研究主要集中在 CD44 介导的内吞作用以促进癌细胞对 HA-NP 的细胞摄取，但我们发现一旦内化，HA-SNP 就可以与其货物一起被转运出细胞。导出的纳米粒子可以被邻近的细胞吸收。这使得 HA-SNP 能够更深入地渗透到肿瘤内部，并在 3D 肿瘤模型中到达更多数量的肿瘤细胞，大概是通过 CD44 介导的胞吞作用和胞吐作用的串联循环。当阿霉素 (DOX) 负载到纳米粒子上时，与游离药物相比，观察到多层肿瘤细胞的渗透性更好，并且针对药物敏感和耐药癌症球体的细胞毒性大大改善。因此，靶向CD44等易于在细胞表面和细胞内部之间循环的受体可以成为增强纳米粒子的肿瘤渗透潜力和通过受体介导的转胞吞作用的药物递送效率的有用策略。
We report that receptor mediated transcytosis can be utilized to facilitate tumor penetration by drug loaded nanoparticles (NPs). We synthesized hyaluronan (HA) coated silica nanoparticles (SNPs) containing a highly fluorescent core to target CD44 expressed on cancer cell surface. Although prior studies have primarily focused on CD44 mediated endocytosis to facilitate cellular uptake of HA-NPs by cancer cells, we discovered that once internalized, the HA-SNPs could be transported out of the cells with its cargo. The exported NPs could be taken up by neighboring cells. This enabled the HA-SNPs to penetrate deeper inside tumor and reach much greater number of tumor cells in 3D tumor models, presumably through tandem cycles of CD44 mediated endocytosis and exocytosis. When doxorubicin (DOX) was loaded onto the NPs, better penetration of multilayered tumor cells was observed with much improved cytotoxicites against both drug sensitive and drug resistant cancer spheroids compared to free drug. Thus, targeting receptors such as CD44 that can readily undergo recycling between cell surface and interior of the cells can become a useful strategy to enhance tumor penetration potential of NPs and the efficiency of drug delivery through receptor mediated transcytosis.
登录
查看更多内容
影响因子：
5.7
作者：
Ho, Won Jin;Pham, Edward A.;Wu, Benjamin M.
通讯作者：
Wu, Benjamin M.
影响因子：
6.7
作者：
El-Dakdouki MH;Puré E;Huang X
通讯作者：
Huang X
DOI：
10.1016/j.jconrel.2012.05.014
发表时间：
2012-08-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Lu W;Xiong C;Zhang R;Shi L;Huang M;Zhang G;Song S;Huang Q;Liu GY;Li C
通讯作者：
Li C
影响因子：
17.1
作者：
Huang K;Ma H;Liu J;Huo S;Kumar A;Wei T;Zhang X;Jin S;Gan Y;Wang PC;He S;Zhang X;Liang XJ
通讯作者：
Liang XJ
影响因子：
3.8
作者：
Kelm, JM;Timmins, NE;Nielsen, LK
通讯作者：
Nielsen, LK