Engineered Lactoferrin Nanoparticle Coronas as a Tunable Platform for Immunomodulation and Antibacterial Function.

Area of Science:

• Biomaterials Science
• Nanotechnology
• Immunology

Background:

• Lactoferrin (Lf) is a glycoprotein with known antimicrobial and immunomodulatory effects.
• Poly(lactic-co-glycolic acid) (PLGA) nanoparticles possess intrinsic anti-inflammatory properties.

Purpose of the Study:

• To engineer a modular nanoparticle platform (PLGA@Lf) by creating a multilayered lactoferrin protein corona on PLGA nanoparticles.
• To investigate the dual functionality of PLGA@Lf in balancing immune activation and suppression for therapeutic applications.

Main Methods:

• Engineered PLGA nanoparticles with a multilayered lactoferrin (Lf) protein corona (PLGA@Lf).
• Characterized nanoparticle properties, including particle size and zeta potential, to confirm corona formation.
• Assessed immune cell stimulation, phagocytosis of Escherichia coli bioparticles, and cytokine levels in LPS-challenged macrophages.
• Evaluated in vitro antimicrobial activity against bioluminescent E. coli.
• Tested the anti-inflammatory efficacy in an in vivo LPS-induced endotoxemia model.

Main Results:

• Lactoferrin adsorbed stably onto PLGA nanoparticles in a concentration-dependent manner, forming a multilayered corona.
• PLGA@Lf stimulated innate immune cells and enhanced E. coli bioparticle phagocytosis.
• Pro-inflammatory cytokine levels were reduced in LPS-challenged macrophages treated with PLGA@Lf.
• Demonstrated robust in vitro inhibition of E. coli growth.
• Significantly reduced plasma TNF-α levels in an in vivo endotoxemia model, indicating enhanced anti-inflammatory effects.

Conclusions:

• PLGA@Lf nanoparticles represent a dual-function nanomaterial platform.
• This platform effectively balances immune stimulation and suppression responses.
• PLGA@Lf offers a promising therapeutic strategy for managing infectious and inflammatory diseases.