Voluntary-Opsonization-Enabled Precision Nanomedicines for Inflammation Treatment

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Immunology

Background:

• Nanomedicines aim to improve drug delivery by targeting specific cells.
• The protein corona, formed on nanomedicines in vivo, often hinders targeted delivery.
• This research explores utilizing the protein corona's natural interactions rather than mitigating them.

Purpose of the Study:

• To engineer nanomedicines that leverage the protein corona for active targeting of inflamed lung tissue.
• To investigate the mechanism of neutrophil recruitment and payload delivery using protein corona-mediated targeting.
• To demonstrate a novel strategy for precision nanomedicine in treating lung inflammation.

Main Methods:

• Molecularly engineered liposomes with inverse phosphocholine lipids were synthesized.
• The formation of the protein corona and its interaction with blood components (iC3b) were analyzed.
• Neutrophil recruitment and migration to inflamed lung tissue were assessed in vivo.
• The efficacy of bacteria killing by liposome-loaded neutrophils was evaluated.

Main Results:

• Liposomes rapidly enriched complement fragment iC3b through "voluntary opsonization."
• This opsonization triggered neutrophil hijacking via complement receptor 3 (CR3) phagocytosis.
• Neutrophil targeting was cell-state dependent, requiring inflammation-activated neutrophils.
• Liposome-loaded neutrophils successfully migrated to inflamed lung tissue and delivered therapeutic payloads, killing bacteria.

Conclusions:

• The protein corona can be repurposed as an active component for precision nanomedicine.
• This approach enables targeted delivery of nanomedicines to inflamed tissues by hijacking immune cells.
• This strategy offers a new platform for developing advanced nanotherapeutics for inflammatory diseases and infections.