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Endogenous Fe^(2+)-activated ROS nanoamplifier for esterase-responsive and photoacoustic imaging-monitored therapeutic improvement

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Nano Research 2022年第2期15卷 907-918页

作者： Sijin Xiang Zhongxiong Fan Ziehen Ye Tianbao Zhu Dao Shi Shefang Ye Zhenqing Hou Xiaolan Chen College of Chemistry and Chemical Engineering&College of Materials State Key Laboratory for Physical Chemistry of Solid SurfacesResearch Center for Nano-Preparation Technology of Fujian Province&Key Laboratory of Biomedical Engineering of Fujian ProvinceXiamen UniversityXiamen 361005China

Chemodynamic therapy(CDT)is well acknowledged as potent reactive oxygen species(ROS)-mediated anticancer ***,the study about labile iron pool(LIP)as endogenous ferrous catalyzer has paved the way for future CDT ***,limited H_(2)O_(2) expression,mild acidity,reduced glutathione(GSH)ablation of ROS,etc.,all require employing alternate peroxo-complex to achieve enhanced CDT *** a non-fenton-type substrate,artesunate(ART)has been utilized as a source of free radicals through decomposition of endoperoxide bridges catalyzed by ferrous ions,nonetheless,the non-tumor-specific delivery,inferior pharmacokinetics,and hydrophobic nature minimize the efficacy of ART in physiological ***,we devise a PPA nanoamplifier by conjugating ART with PEG-functionalized Pd@Pt nanoplates(PP NPs)to form ester linkage,ensuring specific intratumoral esterase-responsive ART ***,the PPA nanoamplifier combines the in situ decomposition of ARTs endoperoxide bridges by Fe^(2+) to superoxide anions(O_(2)^(·-))and peroxidase(POD)-like enzymatic catalysis of endogenous H_(2)O_(2) by PP to hydroxyl radicals(*OH),thus achieving amplified ROS-mediated tumor ***,PPA displays GSH destruction potential,thereby protecting ROS from the cleavage by GSH *** addition,the strong absorption of PPA in near-infrared(NIR)region also endows PPA with photoacoustic property to realize imaging-guided *** short,by taking advantages of the high enrichment and esterase-responsive drug release at tumor sites,PPA amplified ROS signals via dual pathways,killing tumor cells in vitro are inhibiting tumor growth in vivo,thereby realizing high-efficiency non-fenton *** believe our novel anti-tumor strategy based on PPA will broaden the future of ROS-mediated tumor-targeted therapy.

关键词： reactive oxygen species chemodynamic therapy non-fenton tumor microenvironment drug delivery

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