title: Temperature-responsive cationic block copolymers as nanocarriers for gene delivery.
abstract: 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 (PNIPAAMn-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°C, the polyplexes mostly formed structures with size ranging from 100 to 500nm. 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.
authors.affiliation: School of Pharmacy, Department of Pharmaceutics, University of Oslo, P.O. Box 1068, Blindern, N-0316 Oslo, Norway.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Calejo
authors.forename: Ana Maria S
authors.initials: AM
authors.lastname: Cardoso
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Kjøniksen
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Zhu
authors.forename: Catarina M
authors.initials: CM
authors.lastname: Morais
authors.forename: Sverre Arne
authors.initials: SA
authors.lastname: Sande
authors.forename: Ana Luísa
authors.initials: AL
authors.lastname: Cardoso
authors.forename: Maria C Pedroso de
authors.initials: MC
authors.lastname: Lima
authors.forename: Amália
authors.initials: A
authors.lastname: Jurado
authors.forename: Bo
authors.initials: B
authors.lastname: Nyström
mesh_terms: D000180:Acrylic Resins / Q000008:administration & dosage / Q000737:chemistry*; D000327:Adsorption; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry*; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010957:Plasmids; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry*; D013696:Temperature
chemical_list: D000180:Acrylic Resins; D000644:Quaternary Ammonium Compounds; C584203:poly(N-isopropylacrylamide)-block-poly((3-acrylamidopropyl)trimethylammonium chloride); D004247:DNA