Phosphorylcholine-Based Stealthy Nanocapsules Decorating TPGS for Combatting Multi-Drug-Resistant Cancer,ACS Biomaterials Science & Engineering

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Phosphorylcholine-Based Stealthy Nanocapsules Decorating TPGS for Combatting Multi-Drug-Resistant Cancer
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2018-03-19 00:00:00 , DOI: 10.1021/acsbiomaterials.8b00152
Gan Liu ₁ , Hsiang-I Tsai _{2,

3} , Xiaowei Zeng ₁ , Wei Cheng _{2,

3} , Lijuan Jiang _{2,

3} , Hongbo Chen ₁ , Xudong Zhang ₄ , Jinxie Zhang _{2,

3} , Lin Mei ₁

Affiliation

Improving the anticancer efficacy of chemotherapeutics not only demands for efficient delivery into tumor sites, but also always needs to combat the multidrug resistance of cancer. Here we attempted to conquer both these problems by decorating D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) onto a phosphorylcholine-based stealthy nanocapsule. This TPGS-decorated stealthy nanocapsule, referred as nBSA-TPGS-Dox, conjugated anticancer drug doxorubicin (Dox) through an acid-responsive benzoic-imine bond. nBSA-TPGS-Dox was demonstrated to be stable in PBS and exhibited acid-responsive Dox release behavior. In vitro results showed this nanocapsule could be efficiently uptaken by the Dox-resistant HepG2/ADR human liver cancer cells through clathrin-mediated endocytosis and greatly prevented the Dox efflux, causing much more cytotoxicity than free Dox and non-TPGS-decorated nBSA-Dox. Furthermore, nBSA-TPGS-Dox exhibited much prolonged in vivo half-life compared to conventional PEGylated nanoparticles and achieved excellent tumor accumulation. Finally, this TPGS-decorated stealthy nanocapsule performed outstanding suppression of Dox-resistant tumor, much superior than non TPGS-decorated nBSA-Dox and free Dox. Thus, this TPGS-decorated stealthy nanocapsule provides a novel powerful nanomedicine platform for combatting multi-drug-resistant cancer.

中文翻译：

基于磷酸胆碱的隐形纳米胶囊修饰TPGS与多药耐药癌症作斗争。

提高化学治疗剂的抗癌功效不仅需要有效地递送至肿瘤部位，而且始终需要与癌症的多药耐药性作斗争。在这里，我们试图通过将D-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）装饰到基于磷酸胆碱的隐形纳米胶囊上来解决这两个问题。这种被TPGS装饰的隐形纳米胶囊，称为nBSA-TPGS-Dox，通过酸响应性苯甲亚胺键结合了抗癌药物阿霉素（Dox）。nBSA-TPGS-Dox被证明在PBS中稳定，并表现出酸响应性Dox释放行为。体外实验结果表明，这种纳米胶囊可以通过网格蛋白介导的内吞作用被耐Dox的HepG2 / ADR人肝癌细胞有效摄取，并极大地阻止了Dox的外流，与游离Dox和未用TPGS装饰的nBSA-Dox相比，它所引起的细胞毒性要大得多。此外，与常规的聚乙二醇化纳米颗粒相比，nBSA-TPGS-Dox的体内半衰期大大延长，并具有优异的肿瘤蓄积性。最后，这种装饰有TPGS的隐形纳米胶囊对Dox耐药性肿瘤具有出色的抑制作用，远优于未装饰TPGS的nBSA-Dox和游离Dox。因此，这种装饰有TPGS的隐形纳米胶囊提供了一个新颖而强大的纳米药物平台，用于对抗多重耐药性癌症。比非TPGS装饰的nBSA-Dox和自由Dox优越得多。因此，这种装饰有TPGS的隐形纳米胶囊提供了一个新颖而强大的纳米药物平台，用于对抗多重耐药性癌症。比非TPGS装饰的nBSA-Dox和自由Dox优越得多。因此，这种装饰有TPGS的隐形纳米胶囊提供了一个新颖而强大的纳米药物平台，用于对抗多重耐药性癌症。

更新日期：2018-03-19

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