Biomaterials Science 2018-04-06

Polytyrosine nanoparticles enable ultra-high loading of doxorubicin and rapidly enzyme-responsive drug release

Xiaolei Gu, Min Qiu, Huanli Sun, Jian Zhang, Liang Cheng, Chao Deng, Zhiyuan Zhong

Index: 10.1039/C8BM00243F

Full Text: HTML

Abstract

In spite of great significance, few clinically viable nanovehicles possess stable and high anticancer drug loading while fast intracellular drug release. Here, we report that polytyrosine nanoparticles (PTNs) self-assembled from poly(ethylene glycol)-b- poly(L-tyrosine) block copolymer enable ultra-high loading and rapidly enzyme-responsive release of doxorubicin (DOX). Notably, PTNs achieved a remarkably high DOX loading content of 63.1 wt.% likely due to existence of strong π-π stacking between polytyrosine and DOX shown by UV-Vis analysis. PTNs presented also a high loading content of 17.5 wt.% for docetaxel. PTNs exhibited good colloidal stability in 10% FBS but quickly de-stabilized by proteinase K. Interestingly, ca. 90% of DOX was released under 6 U/mL proteinase K in 24 h or in RAW 264.7 cells in 8 h. DOX-loaded PTNs displayed efficient delivery and release of DOX into both RAW 264.7 cells and HCT-116 human colorectal cancer cells, achieving better in vitro antiproliferative effect than the clinically used liposomal DOX formulation. These polytyrosine nanoparticles have appeared to be a potentially viable platform for controlled delivery of anthraquinone anticancer agents.