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

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.