Platelet Membrane-Coated Drug-Loaded Nanoparticles for Dual-Modal Imaging and Photodynamic Therapy in Triple-Negative Breast Cancer

Photodynamic therapy (PDT) has emerged as a promising strategy for cancer treatment; however, its efficacy is hindered by the hypoxic tumor microenvironment. In this study, we designed a bionic nanosystem to enhance oxygen-dependent PDT. The system comprises Fe-doped polydiaminopyridine (Fe-PDAP) nanoenzymes with catalase-like activity, encapsulated with metformin (Met) and indocyanine green (ICG). The surface of the nanoparticles was further coated with platelet membranes (PM), enabling targeted delivery to the tumor site via molecular recognition. In vitro and in vivo studies demonstrated that Fe-PDAP nanoenzymes catalyzed the generation of O₂ from elevated hydrogen peroxide (H₂O₂) while concurrently depleting glutathione (GSH), resulting in increased production of reactive oxygen species (ROS) and enhanced PDT efficacy. Met, acting as a mitochondrial respiratory inhibitor, disrupts complex I of the electron transport chain, thereby reducing ATP levels, inhibiting oxygen (O₂) consumption at the tumor site, and amplifying the PDT effect. Additionally, the bionic nanoparticles (Fe-PDAP-ICG-Met@PM) facilitated both magnetic resonance imaging (MRI) and fluorescence imaging via the Fe-PDAP core and the encapsulated ICG. This study presents an approach to improve PDT and targeted cancer therapy by using bionic nanosystems, providing innovative strategies for effective tumor inhibition.