Issue 12, 2023

Co-delivery of a tumor microenvironment-responsive disulfiram prodrug and CuO2 nanoparticles for efficient cancer treatment

Abstract

Disulfiram (DSF) has been used as a hangover drug for more than seven decades and was found to have potential in cancer treatment, especially mediated by copper. However, the uncoordinated delivery of disulfiram with copper and the instability of disulfiram limit its further applications. Herein, we synthesize a DSF prodrug using a simple strategy that could be activated in a specific tumor microenvironment. Poly amino acids are used as a platform to bind the DSF prodrug through the B–N interaction and encapsulate CuO2 nanoparticles (NPs), obtaining a functional nanoplatform Cu@P–B. In the acidic tumor microenvironment, the loaded CuO2 NPs will produce Cu2+ and cause oxidative stress in cells. At the same time, the increased reactive oxygen species (ROS) will accelerate the release and activation of the DSF prodrug and further chelate the released Cu2+ to produce the noxious copper diethyldithiocarbamate complex, which causes cell apoptosis effectively. Cytotoxicity tests show that the DSF prodrug could effectively kill cancer cells with only a small amount of Cu2+ (0.18 μg mL−1), inhibiting the migration and invasion of tumor cells. In vitro and in vivo experiments have demonstrated that this functional nanoplatform could kill tumor cells effectively with limited toxic side effects, showing a new perspective in DSF prodrug design and cancer treatment.

Graphical abstract: Co-delivery of a tumor microenvironment-responsive disulfiram prodrug and CuO2 nanoparticles for efficient cancer treatment

Supplementary files

Article information

Article type
Paper
Submitted
03 Jan 2023
Accepted
08 May 2023
First published
09 May 2023
This article is Open Access
Creative Commons BY-NC license

Nanoscale Adv., 2023,5, 3336-3347

Co-delivery of a tumor microenvironment-responsive disulfiram prodrug and CuO2 nanoparticles for efficient cancer treatment

F. Cheng, Y. Geng, Y. Liu, X. Nie, X. Zhang, Z. Chen, L. Tang, L. Wang, Y. You and L. Zhang, Nanoscale Adv., 2023, 5, 3336 DOI: 10.1039/D3NA00004D

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