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Lysosomes activating chain reactions against cancer cells with a pH-switched prodrug/procatalyst co-delivery nanosystem
Fu, Jingke1,2; Zhu, Yingchun1
2017
发表期刊Journal of Materials Chemistry B
ISSN20507518
卷号5期号:5页码:996-1004
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.
DOI10.1039/C6TB02820A
EI入藏号20170603327135
EI主题词Nanosystems
EI分类号461.2 Biological Materials and Tissue Engineering - 461.6 Medicine and Pharmacology - 531.1 Metallurgy - 602.1 Mechanical Drives - 761 Nanotechnology - 804 Chemical Products Generally - 804.2 Inorganic Compounds - 933 Solid State Physics
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符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
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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.
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