Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles

Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) within cells proves exceptionally challenging to eradicate using conventional antimicrobials, resulting in recurring infections and heightened resistance. Herein, we reported an innovative mannosylated lipid-coated photodynamic/photothermal calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned as the vehicle for drug delivery, exhibiting preferential uptake by macrophages and facilitating the transport of ICG to intracellular pathogens. The MAN units integrated into MAN-LCaP@ICG could promote binding with MAN residuals on macrophage cells, as evidenced by cellular uptake assays using fluorescence microscopy and flow cytometry. Following its targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm and efficiently eradicate intracellular MRSA by a combination of the lysosome escape capability of CaP and the photodynamic and photothermal therapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA more effectively than LCaP@ICG without MAN units or free ICG in a mouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided a promising direction for human clinical application in combating intracellular infections.