Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem

doi:10.1039/C6TB02820A

	Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem
	Fu, Jingke 1,2; Zhu, Yingchun 1
刊名	Journal of Materials Chemistry B
	2017
卷号	5 期号:5 页码:996-1004
ISSN号	20507518
DOI	10.1039/C6TB02820A
英文摘要	Conventional chemotherapy uses potent toxic drugs to destroy cancer cells and always causes severe systemic toxicity in patients. In this respect, a smart and pH-switched prodrug/procatalyst co-delivery nanosystem is developed which is non-toxic toward normal cells and is inert during its delivery in the vasculature, while responsively functions in acidic lysosomes inside cancer cells. Synthetically, non-toxic artemisinin (ART) was used as the prodrug and loaded into the inner space of hollow mesoporous silica (HMS) nanoparticles (NPs). Subsequently, Fe3O4NPs were efficiently capped onto pore outlets of HMS via acid labile acetal linkers (ART@HMS-Fe3O4). ART@HMS-Fe3O4was stable under neutral conditions (pH 7.4) with almost no leakage of ART. Upon exposure to the acidic lysosomal compartment (pH 3.8-5.0) in cells, the acetal linkers were hydrolyzed which led to sustained release of both ART and Fe3O4NPs. Under the activation of the lysosomal environment, the liberated Fe3O4NPs were metabolized to free iron ions and catalyzed the generation of high amounts of free radicals from the released ART in cells. In vitro cytotoxicity assay revealed excellent anticancer efficacy of this ART/Fe3O4co-delivery nanosystem. The Fe3O4NPs acted both as gatekeepers and procatalysts which inhibited ART from leakage during their delivery, while released ART and activated chain reactions to form free radicals in acidic lysosomes inside cancer cells. We visualize that this lysosomal environment-responsive ART@HMS-Fe3O4nanosystem could serve as an efficient and desirable chemotherapeutic nanosystem for cancer therapy. © The Royal Society of Chemistry.
内容类型	期刊论文
源URL	[http://ir.sic.ac.cn/handle/331005/25580]
专题	中国科学院上海硅酸盐研究所
作者单位	1.Key Laboratory of Inorganic Coating Materials, Shanghai Institute of Ceramics, Chinese Academy of Sciences, 1295 Dingxi Road, Shanghai; 200050, China; 2.School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai; 200240, China
推荐引用方式 GB/T 7714	Fu, Jingke,Zhu, Yingchun. Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem[J]. Journal of Materials Chemistry B,2017,5(5):996-1004.
APA	Fu, Jingke,&Zhu, Yingchun.(2017).Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem.Journal of Materials Chemistry B,5(5),996-1004.
MLA	Fu, Jingke,et al."Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem".Journal of Materials Chemistry B 5.5(2017):996-1004.