Engineered Nanovesicles for the Precise and Noninvasive Treatment of Deep Osteomyelitis Caused by MRSA Infection with...

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Infectious Diseases

Background:

• Hospital-acquired osteomyelitis caused by MRSA is challenging due to poor drug delivery and immune evasion.
• MRSA undermines both innate and adaptive immune responses, complicating treatment.
• Current treatments struggle with deep tissue penetration and combating the immunosuppressive microenvironment.

Purpose of the Study:

• To develop an engineered nanovesicle system for noninvasive treatment of deep osteomyelitis.
• To combine sonodynamic therapy (SDT) with immune modulation for enhanced MRSA clearance.
• To activate the host's antimicrobial immune response against MRSA infections.

Main Methods:

• Engineered macrophage-derived M1 phenotypic microvesicles (M1-MW) encapsulating vancomycin-cross-linked indocyanine green (ICG) micelles (VCG micelles).
• M1-MW were surface-modified with PEGylated mannose for targeted delivery to infection sites.
• Ultrasound-triggered ICG release generated reactive oxygen species (ROS) for MRSA killing, enhanced by vancomycin.

Main Results:

• The VCG@MMW treatment significantly improved survival rates in an osteomyelitis infection model.
• Macrophages were reprogrammed to a pro-inflammatory M1 phenotype, enhancing immune defense.
• The treatment promoted T-cell activation and effective clearance of MRSA infections.

Conclusions:

• The developed VCG@MMW nanovesicles offer a noninvasive and efficient therapeutic strategy for deep osteomyelitis.
• This approach enhances bacterial clearance and reduces recurrence risk by boosting the immune response.
• This study presents a promising nanomedicine strategy for combating challenging MRSA infections.