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

被引:26
作者
Chen, Shi-Xiong [1 ,2 ]
Zhang, Ji [4 ,5 ,6 ,7 ]
Xue, Fengfeng [1 ]
Liu, Wei [4 ,5 ,6 ,7 ]
Kuang, Yichen [1 ,2 ]
Gu, Bingxin [4 ,5 ,6 ,7 ]
Song, Shaoli [4 ,5 ,6 ,7 ]
Chen, Hangrong [1 ,2 ,3 ]
机构
[1] Chinese Acad Sci, Shanghai Inst Ceram, State Key Lab High Performance Ceram & Superfine M, Shanghai 200050, Peoples R China
[2] Univ Chinese Acad Sci, Ctr Mat Sci & Optoelect Engn, Beijing 100049, Peoples R China
[3] Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Chem & Mat Sci, Sublane Xiangshan Rd 1, Hangzhou 310024, Peoples R China
[4] Fudan Univ, Dept Nucl Med, Shanghai Canc Ctr, Shanghai 200032, Peoples R China
[5] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200032, Peoples R China
[6] Fudan Univ, Ctr Biomed Imaging, Shanghai 200032, Peoples R China
[7] Shanghai Engn Res Ctr Mol Imaging Probes, Shanghai 200032, Peoples R China
基金
中国国家自然科学基金;
关键词
Hypoxia-activated prodrugs; Bio-niches; Hypoxia-inducible hydrogels; Antimetastases; THERANOSTIC LIPOSOMES; TUMOR HYPOXIA; CANCER; CHITOSAN; PRODRUG; THERAPY; IMPACT; AQ4N;
D O I
10.1016/j.bioactmat.2022.08.002
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
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.
引用
收藏
页码:86 / 96
页数:11
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