Bioreducible PolymersAs a Determining Factor forPolyplex Decomplexation Rate and Transfection.

Polyplex formation (complexation) and gene release fromthe polyplexes(decomplexation) are major events in polymeric gene delivery; however,the effect of the decomplexation rate on transfection has been rarelyinvestigated. This study employed mixed polymers of poly(L-lysine) (PLL: MW ∼7.4 kDa) and reducible PLL (RPLL) (MW ∼6.7kDa) to design decomplexation rate-controllable PLL100–xRPLLx/pDNA complexes(PRLxpolyplexes). The transfection efficiencyof a model gene (luciferase) in MCF7 and HEK293 cell lines increasedwith increasing x(RPLL content) in the PRLxpolyplexes until peaking at x=2.5 and 10, respectively, after which point transfection efficiencydeclined rapidly. In MCF7 cells, PRL2.5polyplex produced3 or 223 times higher gene expression than PLL or RPLL polyplexes,respectively. Similarly, the transfection efficiency of PRL10polyplex-transfected HEK293 cells was 3.8 or 67 times higher thanthat of PLL or RPLL polyplexes, respectively. The transfection resultswere not apparently related to the particle size, surface charge,complexation/compactness, cellular uptake, or cytotoxicity of thetested polyplexes. However, the decomplexation rate varied by RPLLcontent in the polyplexes, which in turn influenced the gene transfection.The nuclear localization of pDNA delivered by PRLxpolyplexes showed a similar trend to their transfection efficiencies.This study suggests that an optimum decomplexation rate may resultin high nuclear localization of pDNA and transfection. Understandingin decomplexation and intracellular localization of pDNA may helpdevelop more effective polyplexes. [ABSTRACT FROM AUTHOR]