Efficiency of Cytosolic Delivery with Poly(β-amino ester) Nanoparticles is Dependent on the Effective pK_a of the Polymer.

ABSTRACT: The mechanism by which cationic polymers containing titratable amines mediate effective endosomal escape and cytosolic delivery of nucleic acids is not well understood despite the decades of research devoted to these materials. Here, we utilize multiple assays investigating the endosomal escape step associated with plasmid delivery by polyethylenimine (PEI) and poly(β-amino esters) (PBAEs) to improve the understanding of how these cationic polymers enable gene delivery. To probe the role of these materials in facilitating endosomal escape, we utilized vesicle membrane leakage and extracellular pH modulation assays to demonstrate the influence of polymer buffering capacity and effective pK_a on the delivery of the plasmid DNA. Our results demonstrate that transfection with

SUBMITTER: Routkevitch D 

PROVIDER: S-EPMC8034557 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature