Combinatorial Library of Light-Cleavable Lipidoid Nanoparticles for Intracellular Drug Delivery

Synthetic lipid-like molecules (lipidoids) are superior for intracellular delivery of various bioactive cargos. Through incorporating stimuli-responsive linkers, lipidoid nanoparticle-based delivery systems with triggered-release features can be constructed. Enhanced delivery performances have been achieved using disulfide bond-containing bioreducible lipidoids. Herein, we further expand the stimuli-responsive combinatorial lipidoids library by integrating the photocleavable o-nitrobenzyl moiety into the hydrophobic tail of the lipidoids. The structures of these novel lipidoids were confirmed by NMR and MS. The nanoparticles were fabricated through self-assembly procedures, and their photoresponsive behaviors were examined. Light-regulated cargo release and following functionality restoration indicated the potential of the newly developed lipidoid nanoparticles for spatiotemporal delivery.