Tirapazamine encapsulated hyaluronic acid nanomicelles realized targeted and efficient photo-bioreductive cascading cancer therapy  

作　　者：Chunhui Wu Qiuyue Liu Yikun Wang Zhengxin Xie Honglin Huang Ningxi Li Xiaodan Wei Geng Yang Tingting Li Hong Yang Shun Li Xiang Qin Yiyao Liu 

机构地区：[1]Department of Biophysics,School of Life Science and Technology,University of Electronic Science and Technology of China,Chengdu 610054,China [2]TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province,Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,China

出　　处：《Chinese Chemical Letters》2021年第8期2400-2404,共5页中国化学快报（英文版）

基　　金：supported,in part or in whole,by the National Natural Science Foundation of China (Nos.81471785,81671821,11772088,11802056,31800780,11972111,31900940,U19A2006,32071304);the Basic Research Program of Sichuan Science and Technology (Nos.2021YJ0130,2019YJ0183,2019YJ0184);China Postdoctoral Science Foundation (Nos.2018M640904,2019T120831);the Fundamental Research Funds for the Central Universities (No.ZYGX2019J117)。

摘　　要：Currently,architecting a ratio nal and efficient nanoplatform combing with multi-therapeutic modalities is highly obligatory for advanced cancer treatment.In order to remedy the self-limiting hypoxic dilemma of photodynamic therapy(PDT),herein,a facile photosensitizer(i.e.,chlorin e6,Ce6) and bioreductive prodrug(i.e.,tirapazamine,TPZ)-coloaded hyaluronic acid(HA) nanomicelles(denoted as TPZ@HA-Ce6)was developed for the cascading mode of photo-bioreductive cancer therapy.Taking the typical advantage of Ce6 coupled HA conjugate,TPZ was easily and successfully accommodated into the hydrophobic core of HA-Ce6 nanomicelles,yielding [e-mail] showed good dispersibility and stability with the hydrodynamic size of ca.170 nm.It targeted the CD44 overexpressed cancer cells by receptor-mediated endocytosis way and killed them effectively with singlet oxygen and the subsequent TPZ radicals resulting from the oxygen depletion of PDT.The later was further verified by the hypoxia probe in vivo.Using murine mammary carcinoma 4 T1 model,TPZ@HA-Ce6 nanomicelles exhibited cascading and synergistic anticancer effect of PDT and TPZ bioreductive therapy compared with each monotherapy.This work suggests the promising prospect of the hybrid hyaluronic nanomicelles for highly efficient cancer combination treatment.

关 键 词：Hyaluronic acid PHOTOSENSITIZER Bioreductive prodrug Hypoxia Cascading cancer therapy 

分 类 号：R943[医药卫生—药剂学] TB383.1[医药卫生—药学]