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,