PLL/pDNA/P(His-co-DMAEL) ternary complexes: assembly, stability and gene delivery

Abstract

Poly(L-lysine) (PLL) is a kind of biocompatible and biodegradable polycation and can effectively condense plasmid DNA (pDNA) to form nano-scaled complexes. However, the ultra-low gene transfection efficiency limits its wide application in gene delivery. Here, an uncharged functional polymer P(His-co-DMAEL) is synthesized by reversible addition fragmentation transfer (RAFT) polymerization and characterized with ¹H NMR spectrum and size exclusion chromatography (SEC). P(His-co-DMAEL) is assembled with pDNA and PLL to form PLL/pDNA/P(His-co-DMAEL) ternary complexes. Gel shift assays and dynamic light scattering (DLS) tests indicate that the stability of PLL/pDNA/P(His-co-DMAEL) ternary complexes under various conditions is much better than that of PLL/pDNA binary complexes. In vitro transfection shows that the gene transfection efficiency of PLL/pDNA/P(His-co-DMAEL) ternary complexes is much higher than that of PLL/pDNA counterparts and the “gold standard” of gene transfection, poly(ethyleneimine)/pDNA (PEI/pDNA) complexes, especially under serum conditions. Cytotoxicity assays show that PLL/pDNA/P(His-co-DMAEL) ternary complexes have no cytotoxicity. The ternary complexes have advanced the application of PLL as a gene carrier and will have enlightening significance for the development of novel gene and drug delivery carriers.