Eliminating\nIntracellular MRSA via Mannosylated Lipid-Coated\nCalcium Phosphate Nanoparticles

Methicillin-resistant Staphylococcus aureus (MRSA) within cells proves exceptionally challenging to eradicate\nusing conventional antimicrobials, resulting in recurring infections\nand heightened resistance. Herein, we reported an innovative mannosylated\nlipid-coated photodynamic/photothermal calcium phosphate nanoparticle\n(MAN-LCaP@ICG) for eradicating intracellular MRSA. The MAN-LCaP functioned\nas the vehicle for drug delivery, exhibiting preferential uptake by\nmacrophages and facilitating the transport of ICG to intracellular\npathogens. The MAN units integrated into MAN-LCaP@ICG could promote\nbinding with MAN residuals on macrophage cells, as evidenced by cellular\nuptake assays using fluorescence microscopy and flow cytometry. Following\nits targeted accumulation, MAN-LCaP@ICG could enter into the cytoplasm\nand efficiently eradicate intracellular MRSA by a combination of the\nlysosome escape capability of CaP and the photodynamic and photothermal\ntherapeutic effects of ICG. Furthermore, MAN-LCaP@ICG could kill MRSA\nmore effectively than LCaP@ICG without MAN units or free ICG in a\nmouse peritoneal infection model. Therefore, MAN-LCaP@ICG provided\na promising direction for human clinical application in combating\nintracellular infections.