Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Here we report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural erythrocyte membranes, including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. The structure, size and surface zeta potential, and protein contents of the erythrocyte membrane-coated nanoparticles were verified using transmission electron microscopy, dynamic light scattering, and gel electrophoresis, respectively. Mice injections with fluorophore-loaded nanoparticles revealed superior circulation half-life by the erythrocyte-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. Biodistribution study revealed significant particle retention in the blood 72 h following the particle injection. The translocation of natural cellular membranes, their associated proteins, and the corresponding functionalities to the surface of synthetic particles represents a unique approach in nanoparticle functionalization.

Combination chemotherapy and nanoparticle drug delivery are two areas that have shown significant promise in cancer treatment. Combined therapy of two or more drugs promotes synergism among the dif...