Quaternized Poly(4-vinylpyridine)s as Model Gene Delivery Polycations:  Structure−Function Study by Modification of Side Chain Hydrophobicity and Degree of Alkylation

Abstract

To optimize polycation-based gene delivery agents, the influence of molecular characteristics of the polycations on physicochemical properties of polycation/DNA complexes and their relationships to cellular gene transfer need to be understood. With this aim, we have synthesized a series of model polymers based on quaternized poly(4-vinylpyridine)s (CnPVP-beta) with the same DP of 1600 but differing by the number n of methylene groups in N-alkyl ester substituents from 1 to 6 and/or by degree of alkylation beta from 25% to 95%. For polycations CnPVP-95, the efficiency of transfection of a plasmid vector expressing a secreted form of alkaline phosphatase started to be detectable at n = 4, noticeable at n = 5, and again undetectable at n = 6. A decrease in beta of active C5PVP-95 from 95% to 65% resulted in a further noticeable increase of activity with a 9-fold increase for C5PVP-65. This finding was attributed to the proton sponge mechanism due to protonation of non-alkylated pyridine moieties of CnPVP-beta/DNA complexes in slightly acidic media that was supported by the fluorescence quenching assay. The data demonstrate the advantages of partial alkylation of tertiary polyamines with medium-length alkyl agents for preparation of efficient nonviral gene delivery vectors.

Hydrophilic nanoparticles that kill bacteria while sparing mammalian cells reveal the antibiotic role of nanostructures

“…Both silica and P4MVP have been explored for biomedical applications. For example, P4MVP has been studied for gene delivery 35 , 36 ; silica is listed amongst the “generally regarded as safe” substances by the Food and Drug Administration (ID Code: 14808-60-7) 37 , and the long-term effect of silica nanoparticles on human health is still under scrutinization 38 . The metabolization and ultimate fate of NPPBs in human body are not known, but the underlying mechanism of nanostructure-induced transformation of antimicrobial activity revealed using this model system should still have broad implications.…”

Efficient Delivery of Nucleic Acids by Using Modified Polyethylenimine-Based Nanoparticles

“…The higher transfection e±ciency of HPP, AAP, and BPP nanoparticles may also be due to hydrophobicity imparted to the system by the C-6 crosslinkers, leading to an enhanced gene expression. 12 Serum also seemed to have a little e®ect on the transfection e±ciency of PEI nanoparticles ( Fig. 1(b)).…”

Electrostatically Driven Complexation of Liposomes with a Star‐Shaped Polyelectrolyte to Low‐Toxicity Multi‐Liposomal Assemblies

“…The stability of liposome/star complexes in aqueous salt media, i.e., the ability of complexes to dissociate in the presence of various salt concentrations, was traced by the fact that cationic polymers are known to be effective fluorescence quenchers . Thus, we detected formation and dissociation of liposome/star complexes by measuring the fluorescence intensity of a rhodamine‐PE incorporated into the liposomal membrane.…”