Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment

doi:10.1016/j.biomaterials.2020.120329

SIC OpenIR

	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 Publication	BIOMATERIALS
ISSN	0142-9612
Subtype	Article
Abstract	Malignant 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.
DOI	10.1016/j.biomaterials.2020.120329
WOS Keyword	TUMOR MICROENVIRONMENT ; NANOPARTICLES ; IPILIMUMAB ; MUTATIONS ; HYPOXIA ; BRAF
Language	英语
WOS Research Area	Engineering ; Materials Science
Publisher	ELSEVIER SCI LTD
Citation statistics
Document Type	期刊论文
Identifier	http://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).

Files in This Item:
There are no files associated with this item.

If you have any objections to this item, please fill out the form below and the administrator will contact you as soon as possible.
Content:
Email：	*
Institution:
Verification Code:	Refresh

Any comments and suggestions are welcomed.
Title:	*
Content:
Email：	*
Verification Code:	Refresh

中国科学院上海硅酸盐研究所机构知识库