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Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment
Pu, YY; Zhou, BG; Xiang, HJ; Wu, WC; Yin, HH; Yue, WW; Yin, YF; Li, HY; Chen, Y; Xu, HX
2020-11-01
Source PublicationBIOMATERIALS
ISSN0142-9612
SubtypeArticle
AbstractMalignant melanoma is one of the most aggressive skin cancers, posing severe threat to human health. Tyrosinase, overexpressed in melanoma cells, is a specific in-situ weapon to augment the therapeutic efficacy of melanoma-specific treatment by in-situ accelerating the activation of anti-melanoma prodrugs. Herein, we developed a tyrosinase-triggered oxidative stress amplifier, denoted as APAP@PEG/HMnO2, to achieve synergistic chemotherapy and amplified oxidative stress for melanoma-specific treatment. The APAP@PEG/HMnO2 nanosystem was constructed by encapsulating non-toxic prodrug acetaminophen (APAP) into hollow PEG/ HMnO2 nanostructures. After tumor accumulation of APAP@PEG/HMnO2 amplifier, substantial amounts of oxygen (O-2) was generated through reaction between HMnO2 and excessive H2O2 present in tumor environment. Meanwhile, APAP was released at acidic tumor environment and subsequently activated by overexpressed tyrosinase in the presence of O-2 to produce cytotoxic benzoquinone metabolites (AOBQ). On the basis of the combinational effect of AOBQ-triggered reactive oxygen species (ROS) generation and synergistic glutathione (GSH) depletion as promoted by HMnO2 and AOBQ, the APAP@PEG/HMnO2 administration augmented the therapeutic efficacy of chemotherapy by amplifying the intratumoral oxidative stress, thus inducing remarkable cell apoptosis in vitro and tumor suppression in vivo. Therefore, the constructed prodrug nanomedicine represents a prospective tumor-specific therapeutic nanoagent for melanoma treatment.
DOI10.1016/j.biomaterials.2020.120329
WOS KeywordTUMOR MICROENVIRONMENT ; NANOPARTICLES ; IPILIMUMAB ; MUTATIONS ; HYPOXIA ; BRAF
Language英语
WOS Research AreaEngineering ; Materials Science
PublisherELSEVIER SCI LTD
Citation statistics
Document Type期刊论文
Identifierhttp://ir.sic.ac.cn/handle/331005/27656
Collection中国科学院上海硅酸盐研究所
Recommended Citation
GB/T 7714
Pu, YY,Zhou, BG,Xiang, HJ,et al. Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment[J]. BIOMATERIALS,2020.
APA Pu, YY.,Zhou, BG.,Xiang, HJ.,Wu, WC.,Yin, HH.,...&Xu, HX.(2020).Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment.BIOMATERIALS.
MLA Pu, YY,et al."Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment".BIOMATERIALS (2020).
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