期刊
ACTA BIOMATERIALIA
卷 83, 期 -, 页码 334-348出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2018.10.029
关键词
Nitroimidazole; Liposomes; Hypoxia; Targeted delivery; Triggered release; Patient-derived xenograft
资金
- National Natural Science Foundation of China [81401506]
- Natural Science Foundation of Jiangsu Province of China (China) [BK20161283]
- Jiangsu Province Six Summit Talent Foundation (China) [2016-YY-061]
- Applied Basic Research Project Foundation of Nantong (China) [MS12015047, MS12016024, MS22016066]
- Jiangsu Overseas Visiting Scholar Program for University Prominent Young & Middle-aged Teachers and Presidents (China)
Hypoxia is not merely a tumor microenvironment byproduct, but rather an active participant in tumor development, invasion, and metastasis. Hypoxia contributes to poor outcomes in tumor treatment and has currently emerged as an important therapeutic target. In this work, a facile hypoxia-responsive liposomal drug delivery system was developed by incorporating derivatized nitroimidazole into liposome membranes. Under hypoxic conditions, hypoxia-induced reductive metabolism of the nitroimidazole derivative facilitated disassembly of the liposomes for triggered drug release. The liposomes showed high sensitivity to hypoxia, even at the cellular level, and could release payload in an oxygen-dependent manner, leading to high cytotoxicity in hypoxic conditions. In vivo fluorescence imaging revealed that there was a selective release of the liposomes at the hypoxic tumor site. As a result, the liposomes exhibited enhanced therapeutic efficacy in treating a hypoxic tumor in both cell line-derived and clinically relevant patient-derived xenograft models. Thus, hypoxia-responsive liposomes are a promising drug delivery system for hypoxia targeted tumor therapy. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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