Temperature-controlled properties of DNA complexes with poly(ethylenimine)-graft-poly(N-isopropylacrylamide).
End-functionalized poly(N-isopropylacrylamide) (PNIPA) was synthesized by living free radical polymerization and conventional free radical polymerization and was used to prepare graft copolymers with poly(ethylenimine) (PEI). The copolymers exhibited lower critical solution temperature (LCST) behavior between 30 and 32 degrees C and formed complexes with plasmid DNA. The LCST of the copolymers in the DNA complexes increased slightly to approximately 34-35 degrees C. Cytotoxicity of the copolymers was evaluated by measuring lactate dehydrogenase (LDH) release from cells. The copolymers exhibited temperature-dependent toxicity, with higher levels of LDH release observed at temperatures above the LCST. Cellular uptake and transfection activity of the DNA complexes with the PEI-g-PNIPA copolymers were lower than those of the control PEI/DNA complexes at temperature below the LCST but increased to the PEI/DNA levels at temperatures above the LCST.
Bisht
Harender S
HS
Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan 48202, USA.
Manickam
Devika Soundara
DS
You
Yezi
Y
Oupicky
David
D
D000180:Acrylic Resins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000737:chemistry / Q000378:metabolism; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D013696:Temperature; D013997:Time Factors
D000180:Acrylic Resins; C511369:poly(ethylenimine)-graft-poly(N-isopropylacrylamide); D049452:Green Fluorescent Proteins; D004247:DNA; D007770:L-Lactate Dehydrogenase; D008156:Luciferases