Bacteria-mimetic nanomedicine for targeted eradication of intracellular MRSA

Area of Science:

• Biomaterials Science
• Nanotechnology
• Infectious Diseases

Background:

• Intracellular bacteria like methicillin-resistant Staphylococcus aureus (MRSA) infections are a major health concern.
• Existing nanomedicines struggle with macrophage uptake and retention, limiting efficacy against intracellular pathogens.
• Effective strategies are needed to enhance antibacterial agent delivery within infected host cells.

Purpose of the Study:

• To develop novel bacterial membrane-coated mesoporous silica nanoparticles (MSN) for enhanced intracellular delivery of vancomycin (Van).
• To investigate the self-aggregation and host-guest interaction-driven retention of these nanoparticles within macrophages.
• To evaluate the efficacy of vancomycin-loaded MSN against intracellular MRSA and associated inflammation.

Main Methods:

• Fabrication of bacterial membrane-coated MSN loaded with vancomycin.
• Utilizing cucurbit[7]uril-adamantane host-guest interactions for nanoparticle self-aggregation.
• In vitro and in vivo assessment of nanoparticle uptake, retention, antibacterial activity, and anti-inflammatory effects.

Main Results:

• Nanoparticles demonstrated specific recognition and internalization by macrophages.
• Self-aggregated MSN clusters showed slow clearance and extended retention within infected macrophages.
• Acid-triggered vancomycin release from MSN aggregates effectively eradicated intracellular MRSA.
• Significant alleviation of inflammation in both in vitro and in vivo models.

Conclusions:

• Bacterial membrane-coated MSN offer a promising strategy for treating drug-resistant intracellular bacterial infections.
• Nanoparticle self-aggregation and host-guest interactions enhance intracellular drug retention and efficacy.
• This approach provides new insights for designing advanced antibacterial nanomaterials.