In situ forming oxygen/ROS-responsive niche-like hydrogel enabling gelation-triggered chemotherapy and inhibition of metastasis  

作　　者：Shi-Xiong Chen Ji Zhang Fengfeng Xue Wei Liu Yichen Kuang Bingxin Gu Shaoli Song Hangrong Chen 

机构地区：[1]State Key Laboratory of High Performance Ceramics and Superfine Microstructures,Shanghai Institute of Ceramics,Chinese Academy of Sciences,Shanghai,200050,PR China [2]Center of Materials Science and Optoelectronics Engineering,University of Chinese Academy of Sciences,Beijing,100049,PR China [3]School of Chemistry and Materials Science,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Sub-lane Xiangshan Road 1,Hangzhou,310024,PR China [4]Department of Nuclear Medicine,Fudan University Shanghai Cancer Center,Shanghai,200032,PR China [5]Department of Oncology,Shanghai Medical College,Fudan University,Shanghai,200032,PR China [6]Center for Biomedical Imaging,Fudan University,Shanghai,200032,PR China [7]Shanghai Engineering Research Center of Molecular Imaging Probes,Shanghai,200032,PR China

出　　处：《Bioactive Materials》2023年第3期86-96,共11页生物活性材料（英文）

基　　金：National Key Research and Development Program of China(Grant No.2021YFB3801001);National Natural Science Foundation of China(Grant Nos.32030061);Key Program for Basic Research of Shanghai(Grant No.19JC1415600,21JC1406000);All the animal experiments were performed with the approval of the Fudan University Experimental Animal Center;animal biomedical research authorization numbered is 2020-Cancer hospital-JS220.

摘　　要：Though the development of the diverse hypoxia-activated prodrugs(HAPs)has made great progresses in the last several decades,current cancer therapy based on HAPs still suffers many obstacles,e.g.,poor therapeutic outcome owing to hard deep reaching to hypoxic region,and the occurrence of metastasis due to hypoxia.Inspired by engineered niches,a novel functional chitosan polymer(CS-FTP)is synthesized for construction of a hydrogel-based bio-niche(CS-FTP-gel)in aiming at remodeling tumor hypoxic microenvironment.The CS-FTP polymers are crosslinked to form a niche-like hydrogel via enzyme-mediated oxygen-consumable dimerization after injected into tumor,in which a HAP(i.e.,AQ4N)could be physically encapsulated,resulting in enhanced tumor hypoxia to facilitate AQ4N-AQ4 toxic transformation for maximizing efficacy of chemotherapy.Furthermore,Pazopanib(PAZ)conjugated onto the CS backbone via ROS-sensitive linker undergoes a stimuli-responsive release behavior to promote antiangiogenesis for tumor starvation,eventually contributing to the inhibition of lung metastasis and synergistic action with AQ4N-based chemotherapy for an orthotopic 4T1 breast tumor model.This study provides a promising strategy for hypoxia-based chemotherapy and demonstrates an encouraging clinical potential for multifunctional hydrogel applicable for antitumor treatment.

关 键 词：Hypoxia-activated prodrugs Bio-niches Hypoxia-inducible hydrogels Antimetastases 

分 类 号：TQ427.26[化学工程]