Disulfiram-Loaded PLGA nanoparticles modified with a Phenyl borate chitosan Conjugate enhance hepatic carcinoma treatment

Abstract

Disulfiram (DSF), which has been traditionally used to treat alcoholism, has been shown to inhibit tumor growth, indicating its potential as an anticancer agent. However, its development and application are hindered by its poor water solubility, instability in physiological environments, and low bioavailability. In this study, phenylboronic acid-chitosan (PBA-CS) grafts were synthesized using the carbodiimide method. PBA-CS-modified DSF PLGA nanoparticles (DSF@PBA-CS-PLGA NPs) were constructed by coating the nanoparticle surfaces with PBA-CS to improve the stability of DSF in physiological environments and enhance its anti-tumor effects. The structures of PBA-CS and the DSF@PBA-CS–PLGA NPs were confirmed using FTIR UVs, DLS, ELS, TEM, ¹HNMR, DSC. Our in vitro degradation experiments showed that PBA-CS-PLGA NPs significantly improved the stability of DSF in physiological environments. Cell experiments showed that PBA-CS–PLGA NPs improved drug uptake and strongly inhibited HepG2 cell migration. A mouse tumor model was established using Dutch H22 cells. DSF@PBA-CS-PLGA NPs showed better tumor-targeting ability than DSF@PLGA NPs, with a tumor inhibition rate of more than 60%, and they induced apoptosis and inhibited neovascularization in mouse tumor tissues. Both the in vitro and in vivo experiments indicated that the DSF@PBA-CS-PLGA NPs overcame the limitations of DSF, improving the dissolution rate and stability of the drug, ultimately offering low toxicity, sustained release, and targeted delivery. These findings demonstrated the potential of DSF@PBA-CS-PLGA NPs for hepatic carcinoma therapy.