Hypoxia-degradable and long-circulating zwitterionic phosphorylcholine-based nanogel for enhanced tumor drug delivery  

作　　者：Shaojun Peng Boshu Ouyang Yongjie Xin Wei Zhao Shun Shen Meixiao Zhan Ligong Lu 

机构地区：[1]Zhuhai Precision Medical Center,Zhuhai Interventional Medical Center,Zhuhai People’s Hospital(Zhuhai Hospital Affiliated with Jinan University),Zhuhai 519000,China [2]The Institute for Translational Nanomedicine,Shanghai East Hospital,Tongji University School of Medicine,Shanghai 200120,China [3]Zhejiang Cancer Hospital,Institute of Cancer Research,Hangzhou 310012,China [4]Central Laboratory,First Affiliated Hospital,Institute(College)of Integrative Medicine,Dalian Medical University,Dalian 116021,China

出　　处：《Acta Pharmaceutica Sinica B》2021年第2期560-571,共12页药学学报（英文版）

基　　金：financially supported by the National Key Research and Development Program of China(No.2017YFA0205200);the National Natural Science Foundation of China(Grant No.81903165 and 81901857);the Chinese Postdoctoral Foundation(Grant No.2019M663361,China)

摘　　要：Tumor microenvironment has been widely utilized for advanced drug delivery in recent years,among which hypoxia-responsive drug delivery systems have become the research hotspot.Although hypoxia-responsive micelles or polymersomes have been successfully developed,a type of hypoxia-degradable nanogel has rarely been reported and the advantages of hypoxia-degradable nanogel over other kinds of degradable nanogels in tumor drug delivery remain unclear.Herein,we reported the synthesis of a novel hypoxia-responsive crosslinker and the fabrication of a hypoxia-degradable zwitterionic poly(phosphorylcholine)-based(HPMPC)nanogel for tumor drug delivery.The obtained HPMPC nanogel showed ultra-long blood circulation and desirable immune compatibility,which leads to high and long-lasting accumulation in tumor tissue.Furthermore,HPMPC nanogel could rapidly degrade into oligomers of low molecule weight owing to the degradation of azo bond in hypoxic environment,which leads to the effective release of the loaded drug.Impressively,HPMPC nanogel showed superior tumor inhibition effect both in vitro and in vivo compared to the reduction-responsive phosphorylcholine-based nanogel,owing to the more complete drug release.Overall,the drug-loaded HPMPC nanogel exhibits a pronounced tumor inhibition effect in a humanized subcutaneous liver cancer model with negligible side effects,which showed great potential as nanocarrier for advanced tumor drug delivery.

关 键 词：Hypoxia-degradable Zwitterionic nanogel Long blood circulation Drug release Drug delivery 

分 类 号：R943[医药卫生—药剂学]