Extending the in vivo residence time of macrophage membrane-coated nanoparticles through genetic modification

Summary

This preclinical study uses genetic modification of the membrane-source cell to keep macrophage-mimicking nanoparticles in the body for longer. Although macrophage membrane coatings support delivery and biological neutralization, circulating particles can be marked by opsonins and removed through phagocytosis. The researchers engineered macrophages to express chains of proline, alanine, and serine residues, then used those altered membranes to coat nanoparticles. The PAS layer provided additional protection against recognition and uptake. Compared with particles carrying unmodified macrophage membrane, the engineered formulation had longer residence after intravenous administration and after direct introduction into the trachea. Prolonged exposure was accompanied by stronger inhibition of inflammatory cytokines in mouse models of lipopolysaccharide-induced lung injury and sublethal endotoxemia, respectively. The principal finding is that a genetically encoded surface polymer can alter the pharmacological persistence of a membrane-coated particle across two delivery routes and improve its downstream anti-inflammatory function. This offers a potentially general method for tuning other cellular coatings. The abstract does not quantify circulation or lung residence, define the cytokines and disease outcomes, compare established stealth materials, or assess immunogenicity and long-term safety of PAS-modified membranes.