Temperature-responsive cationic block copolymers as nanocarriers for gene delivery

Cationic block copolymers have been regarded as promising alternatives to the use of viral vectors for gene delivery. In this work, poly(N-isopropylacrylamide)(n)-block-poly((3-acrylamidopropyl)trimethylammonium chloride)(m) (PNIPAAM(n)-b-PAMPTMA(+)(m)) block copolymers with n = 48 or 65 and m = 6, 10 or 20 were synthesized and evaluated in terms of their potential for in vitro transfection of HeLa cells. These block copolymers collapse above a phase transition temperature, allowing the entrapment of the DNA molecules they are adsorbed to. The transfection efficiency increased with polymer concentration and was higher in the presence of a long PNIPAAM block and for a short charged block. In general, increasing the length of the charged block decreased the transfection efficiency. Additionally, polymer-DNA complexes (polyplexes) formed at lower polymer/DNA charge ratios caused lower cell toxicity levels. All polymers were shown to efficiently protect the DNA, even when they were present at low concentrations. At 37 degrees C, the polyplexes mostly formed structures with size ranging from 100 to 500 nm. The results also showed that the thermoresponsive contraction of PNIPAAM causes the charged block segments to be pressed out to the surface. The formation of compact structures seems to be a key factor in achieving high transfection efficiency. (C) 2013 Elsevier B.V. All rights reserved.