Issue 45, 2021

A tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

Abstract

Tumor-selective drug delivery could enhance anticancer efficacy and avoid drug side effects. However, because of tumor heterogeneity, current nanoparticle-based drug delivery systems rarely improve clinical outcomes significantly, commonly only reducing systemic toxicity. In this work, a new tumor-specific, tyrosinase-responsive cascade amplification release nanoparticle (TR-CARN) was developed to fulfill the needs for tumor-specific drug delivery and high efficacy cancer treatment. Tyrosinase (Tyr) is specifically expressed in melanomas and can catalyze acetaminophen (APAP) to increase reactive oxygen species (ROS). It was therefore utilized here to initiate the ROS amplification procedure. In TR-CARN, a ROS-responsive prodrug BDOX was loaded into an amphiphilic polymer, and APAP was linked to the polymer through a ROS-cleavable thioether bond. TR-CARN caused reduced side effects during the delivery because of the low toxicity of BDOX. Once TR-CARN entered into the tumor, endogenous ROS triggered initial APAP and BDOX release. Tyr-mediated ROS synthesis by APAP then accelerated APAP and BDOX release and toxification. Consequently, TR-CARN achieved melanoma-specific treatment of high efficacy through the cascade amplification strategy with enhanced biosafety.

Graphical abstract: A tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

Supplementary files

Article information

Article type
Paper
Submitted
30 Aug 2021
Accepted
08 Oct 2021
First published
11 Oct 2021

J. Mater. Chem. B, 2021,9, 9406-9412

A tyrosinase-responsive tumor-specific cascade amplification drug release system for melanoma therapy

D. Li, X. Zhou, W. Zhang, H. Xu, B. Xiao, X. Xu, X. Shi, R. Wang, S. Yao, Z. Zhou, J. Gao, H. Hu, Y. Shen, N. K. H. Slater and J. Tang, J. Mater. Chem. B, 2021, 9, 9406 DOI: 10.1039/D1TB01893K

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