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Eliminating Intracellular MRSA via Mannosylated Lipid-Coated Calcium Phosphate Nanoparticles
Xiangjun Chen1, Xiaoyi Shi1, Xiao Liu1
1School of Pharmacy, Shandong Engineering Research Center of New-Type Drug Loading & Releasing Technology and Preparation, Binzhou Medical University, 346 Guanhai Road, Yantai 264003, P. R. China.
Abstract:
Methicillin-resistant Staphylococcus aureus (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.
Insights
A novel nanoparticle effectively eradicates intracellular Methicillin-resistant Staphylococcus aureus (MRSA). This mannosylated lipid-coated nanoparticle targets macrophages, delivering a therapeutic agent for enhanced killing of persistent MRSA infections.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Infectious Diseases
Background:
- Intracellular Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant challenge due to its resistance to conventional antibiotics.
- Recurrent infections and increasing antimicrobial resistance necessitate novel therapeutic strategies.
Purpose of the Study:
- To develop and evaluate a mannosylated lipid-coated calcium phosphate nanoparticle (MAN-LCaP@ICG) for eradicating intracellular MRSA.
- To investigate the targeted delivery and therapeutic efficacy of MAN-LCaP@ICG against MRSA.
Main Methods:
- Synthesis of mannosylated lipid-coated calcium phosphate nanoparticles encapsulating indocyanine green (ICG).
- In vitro cellular uptake studies using fluorescence microscopy and flow cytometry to assess macrophage targeting.
- In vivo efficacy evaluation in a mouse peritoneal infection model.
Main Results:
- MAN-LCaP@ICG demonstrated enhanced uptake by macrophages due to mannose-receptor interactions.
- The nanoparticles effectively delivered ICG to intracellular MRSA, leading to pathogen eradication via photodynamic and photothermal therapy.
- MAN-LCaP@ICG showed superior efficacy in clearing MRSA compared to control formulations in vivo.
Conclusions:
- Mannosylated lipid-coated nanoparticles offer a promising platform for targeted delivery of therapeutic agents against intracellular bacterial infections.
- MAN-LCaP@ICG presents a viable strategy for combating challenging MRSA infections, with potential for clinical translation.
