Poly(l-glutamic acid) augments the transfection performance of lipophilic polycations by overcoming tradeoffs among cytotoxicity, pDNA delivery efficiency, and serum stability.

ABSTRACT: Polycations are scalable and affordable nanocarriers for delivering therapeutic nucleic acids. Yet, cationicity-dependent tradeoffs between nucleic acid delivery efficiency, cytotoxicity, and serum stability hinder clinical translation. Typically, the most efficient polycationic vehicles also tend to be the most toxic. For lipophilic polycations-which recruit hydrophobic interactions in addition to electrostatic interactions to bind and deliver nucleic acids-extensive chemical or architectural modifications sometimes fail to resolve intractable toxicity-efficiency tradeoffs. Here, we employ a facile post-synthetic polyplex surface modification strategy wherein poly(l-glutamic acid) (PGA) rescues toxicity, inhibits hemolysis, and prevents serum inhibition of lipophilic polycation-mediated p

SUBMITTER: Sekar RP 

PROVIDER: S-EPMC11255917 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature