Functional Tailoring of Polydopamine/Mn3O4 Nanoparticle Composites with Glutathione-Responsive Dissociation for Drug Delivery

Abstract

Polydopamine (PDA) has demonstrated remarkable potential in the biomedical field due to its excellent biocompatibility. Exploring functional PDA can further enhance its application in drug delivery systems (DDS). In this study, we present a facile one-pot fabrication method for GSH- responsive PDA nanoparticles (NPs) through in situ formation of Mn₃O₄. Following PEGylation, the resultant functional DDS ((Mn₃O₄/PDA)-PEG) was used to encapsulate the chemotherapy drug doxorubicin (DOX), yielding DOX-loaded (Mn₃O₄/PDA)-PEG NPs. The findings indicate that the incorporation of Mn₃O₄ significantly enhances the responsiveness of PDA to tumor microenvironment stimuli, enabling GSH-triggered controlled drug release at specific sites. Moreover, Mn₃O₄ effectively prevents premature drug release under normal physiological conditions. Consequently, leveraging the GSH-responsiveness of the DDS facilitates the disassembly of PDA NPs, thereby markedly improving the bioavailability and therapeutic efficacy of chemotherapy drugs. This work encourages us to continue to prepare polydopamine materials with multiple functions through rational additive substances to improve the bioavailability of chemotherapy drugs.