Disulfide-cross-linked PEG-block-polypeptide nanoparticles with high drug loading content as glutathione-triggered anticancer drug nanocarriers

Yu Fon Chen, Chien Hsiang Chang, Ching Yu Lin, Li Fang Lin, Ming Lung Yeh, Jeng Shiung Jan

研究成果: Article同行評審

13 引文 斯高帕斯(Scopus)

摘要

The development of stimuli-responsive drug carrier systems enabling to deliver high doses of anti-cancer drugs to tumor tissues is still urgently needed. In this study, we report the preparation of reduction-responsive methoxypolyethylene glycol-block-(poly(L-lysine)-co-poly(L-tyrosine)) (mPEG-b-(PLL-co-PLY)) nanoparticles (NPs) exhibiting sizes smaller than 100 nm and high drug loading content (DLC) of doxorubicin (DOX) by selecting the Lys and Tyr residues as the polypeptide building blocks. The disulfide-cross-linked mPEG-b-(PLL-co-PLY) assemblies with sizes can be tuned by varying the polypeptide composition followed by subsequent disulfide-cross-linking. Cytotoxicity assays showed that the Dox-loaded NPs exhibited efficient cell internalization and proliferation inhibition toward cancer cells, whereas the copolymers exhibited low hemolysis to human red blood cells and excellent biocompatibility to both normal and cancer cells. The enhanced internalization and cytotoxicity of DOX-NPs can be possible due to their small size and their reduction-responsive property. Anticancer studies using C57BL/6 mice bearing LLC tumor model showed that the DOX-loaded NPs significantly suppressed tumor growth and prolonged the survival of tumor-bearing mice without obvious body weight loss and damage to major organs. This approach provides a platform for developing stimuli-responsive, polypeptide-based drug delivery systems with high DLC for cancer treatment.

原文English
頁(從 - 到)172-181
頁數10
期刊Colloids and Surfaces B: Biointerfaces
165
DOIs
出版狀態Published - 2018 五月 1

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 表面和介面
  • 物理與理論化學
  • 膠體和表面化學

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