Biomimetic Long-Circulating Nanoparticles for Combinatorial Drug Delivery

Efforts to extend nanoparticle residence time in vivo have inspired many strategies in particle surface modifications to bypass macrophage uptake and systemic clearance. Herein I report a top-down biomimetic approach in particle functionalization by coating biodegradable polymeric nanoparticles with natural red blood cell (RBC) membranes including both membrane lipids and associated membrane proteins for long-circulating cargo delivery. This approach aims to camouflage the nanoparticle surface with the erythrocyte exterior for long circulation while retaining the applicability of the polymeric core. In vivo results revealed superior pharmacokinetics and biodistribution by the RBC-mimicking nanoparticles as compared to control particles coated with the state-of-the-art synthetic stealth materials. I will also report several new strategies for nanoparticle-based combination chemotherapy by concurrently incorporating two different types of drugs into a single polymeric nanoparticle with ratiometric control over the loading of the two drugs. The cytotoxicity of these dual-drug carrying nanoparticles was compared with their cocktail mixtures of single-drug loaded nanoparticles and showed superior therapeutic effect.