Strategies for improving endosomal escape of polymeric nanoparticles

While nanoparticle systems serve as a promising platform for the delivery of small molecule, nucleic acid, and protein-based therapeutics for a variety of diseases, their therapeutic efficacy is currently constrained by poor endosomal escape once internalized. Successful nanoparticle-based delivery entails effective endosomal escape and subsequent cytosolic release of therapeutic cargo, thus it is imperative that nanoparticle platforms integrate endosomal escape moieties into their synthesis. This review will discuss synthetic strategies for nanoparticles that improve endosomal escape, with a focus on strategies compatible with polymer-based nanoparticles. Recent advancements in polymer, small molecule, and peptide-based strategies will be presented to analyze the successes and limitations of these strategies through a translational lens.   

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