Modulating Lipid-Polymer Nanoparticles' Physicochemical Properties to Alter Macrophage Uptake

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cell Biology

Background:

• Macrophage nanoparticle uptake is crucial for drug delivery and immunotherapy.
• Physicochemical properties of nanoparticles significantly influence their interaction with macrophages.

Purpose of the Study:

• To investigate the impact of size, stiffness, and lipid composition on lipid-polymer nanoparticle (LPNP) uptake by macrophages.
• To elucidate the relationship between nanoparticle characteristics and macrophage polarization in uptake.

Main Methods:

• Synthesized a library of LPNPs with varying diameters (232-812 nm), storage modulus (21.2-287 kPa), and phosphatidylserine content (0-20%).
• Quantified LPNP uptake in murine bone marrow-derived macrophages.
• Assessed uptake differences in M1 and M2 polarized macrophages.

Main Results:

• Stiff, large LPNPs with phosphatidylserine exhibited 9.3x to 166x higher uptake compared to other formulations.
• Phosphatidylserine-containing LPNPs were preferentially taken up by M2 macrophages.
• LPNPs lacking phosphatidylserine were primarily internalized by M1 macrophages.
• Uptake was predominantly mediated by phagocytosis, irrespective of other endocytic pathways.

Conclusions:

• Nanoparticle size, stiffness, and surface chemistry (phosphatidylserine) synergistically enhance macrophage uptake.
• Tailoring LPNP physicochemical properties can modulate their interaction with specific macrophage subtypes.
• Findings provide a foundation for optimizing nanoparticle design for targeted cellular delivery.