Thermo-responsive “hairy-rod” polypeptides for smart antitumor drug delivery
Literature Information
Jianxun Ding, Di Li, Chunsheng Xiao, Xiuli Zhuang, Xuesi Chen
A series of thermo-responsive “hairy-rod” polypeptides was efficiently synthesized by grafting of azide-terminated (co)polymers of 2-(2-methoxyethoxy)ethyl methacrylate (MEO2MA) or 2-(2-(2-methoxyethoxy)ethoxy)ethyl methacrylate (MEO3MA) (i.e., N3-PMEOiMA) onto poly(γ-propargyl-L-glutamate) (PPLG) through a “click” reaction. The thermo-responsiveness and secondary structure of the resultant polypeptides (i.e. PLG-g-PMEOiMA) were shown to be dependent on the MEO2MA : MEO3MA ratio in PMEOiMA side chains. PLG40-g-P(MEO2MA18-co-MEO3MA9) (P2) and PLG40-g-P(MEO2MA7-co-MEO3MA18) (P4) with lower critical solution temperatures at 25.6 and 34.8 °C, and cloud points at 26.9 and 35.6 °C in physiological saline, respectively, were selected to self-assemble into micelles for doxorubicin (DOX) loading and release. In vitro DOX release from DOX-loaded micelles could be accelerated by a decrease of temperature and pH. Confocal laser scanning microscopy and flow cytometry confirmed the efficient internalization and intracellular DOX release of DOX-loaded micelles towards HeLa cells (a human cervical carcinoma cell line). In vitro methyl thiazolyl tetrazolium assays revealed that the polypeptides were cytocompatible, and DOX-loaded micelles showed efficient cellular proliferation inhibition. Hemolysis tests indicated that micelles were hemocompatible, and the encapsulation with polypeptides significantly reduced the hemolysis ratio of DOX. Therefore, the thermo-responsive polypeptide micelles, which are stable in physiological condition while releasing payloads in the acidic intracellular microenvironment, are promising for smart drug delivery.
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