Vitamin B12-conjugated sericin micelles for targeting CD320-overexpressed gastric cancer and reversing drug resistance
Vitamin B12-conjugated sericin micelles for targeting CD320-overexpressed gastric cancer and reversing drug resistance
复制标题
维生素 B12 缀合丝胶胶束用于靶向 CD320 过表达的胃癌并逆转耐药性
DOI：
10.2217/nnm-2018-0321
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发表时间：
2019-02-01
期刊：
影响因子：
5.5
通讯作者：
Hu, Yanfeng
中科院分区：
文献类型：
--
作者：
Guo, Weihong;Deng, Lizhi;Hu, Yanfeng
目的：我们前期的研究引入了丝胶胶束来逆转耐药性。然而，这些胶束不能选择性地结合胃癌（GC）细胞。我们开发了用于靶向 GC 治疗的维生素 B12 (VB12) 结合丝胶胶束。材料和方法：我们使用 VB12、丝胶、合成聚（-苄基-L-谷氨酸）(PBLG) 和紫杉醇 (PTX) 来开发 VB12 缀合和 PTX 负载的胶束 (VB12-丝胶-PBLG-PTX)。然后我们探讨了它们的理化特性、细胞摄取和抗肿瘤机制。结果：VB12-丝胶-PBLG-PTX胶束粒径适宜、分散性好、生物安全。在转钴胺素 II (CD320) 受体介导的内吞作用之后，这些吞咽的胶束具有 GC 靶向性和增强的细胞摄取能力，改变线粒体跨膜电位/凋亡途径并逆转耐药性。结论：VB12-丝胶-PBLG-PTX胶束是GC靶向临床应用的有前景的材料。
Aim: Our previous research has introduced sericin micelles to reverse drug resistance. However, these micelles could not selectively bind to gastric cancer (GC) cells. We developed vitamin B12 (VB12) conjugated sericin micelles for targeted GC therapy. Materials & methods: We used VB12, sericin, synthetic poly(-benzyl-L-glutamate) (PBLG) and paclitaxel (PTX) to develop VB12-conjugated and PTX-loaded micelles (VB12-sericin-PBLG-PTX). Then we explored their physicochemical properties, cellular uptake and antitumor mechanism. Results: VB12-sericin-PBLG-PTX micelles were proved to be of appropriate particle size, have good dispersion and are bio-safe. Following transcobalamin II (CD320)-receptor-mediated endocytosis, these swallowed micelles with GC-targeting and enhanced cellular uptake abilities, alter mitochondrial transmembrane potential/apoptosis pathway and reverse drug resistance. Conclusion: VB12-sericin-PBLG-PTX micelles are promising materials for GC-targeted clinical applications.