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

Tyrosinase-activated prodrug nanomedicine as oxidative stress amplifier for melanoma-specific treatment. Biomaterials. 2020 Aug 15;259:120329 Authors: Pu Y, Zhou B, Xiang H, Wu W, Yin H, Yue W, Yin Y, Li H, Chen Y, Xu H 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 (O2) 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 O2 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 a...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research