Thiol‐Disulfide Exchange as a Route for Endosomal Escape of Polymeric Nanoparticles
Pintu Kanjilal, Kingshuk Dutta, S. Thayumanavan
Abstract
Endosomal entrapment has remained the major bottleneck for cytosolic delivery of nanoparticle-based delivery systems. Uncovering fundamentally new pathways for endosomal escape is therefore highly sought. Herein, we report that disulfide bonds can enhance endosomal escape through contacts with cellular exofacial thiols, in addition to facilitating cellular uptake. Our results are supported through comparative analysis of polymeric nanogels with variable accessibility to disulfide bonds by placing these functionalities at the core or the shell of the nanogels. The findings here inform future chemical design of delivery vehicles.
Topics & Concepts
EndosomeDisulfide bondNanoparticleChemistryNanotechnologyThiolCytosolCross-presentationMaterials scienceOrganic chemistryBiochemistryCellIn vitroCytotoxic T cellEnzymeAntigen-presenting cellRNA Interference and Gene DeliveryAdvanced biosensing and bioanalysis techniquesNanoparticle-Based Drug Delivery