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Spermine‐ alt ‐poly(ethylene glycol) polyspermine as a safe and efficient aerosol gene carrier for lung cancer therapy
Author(s) -
Kim YouKyoung,
Cho ChongSu,
Cho MyungHaing,
Jiang HuLin
Publication year - 2014
Publication title -
journal of biomedical materials research part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.849
H-Index - 150
eISSN - 1552-4965
pISSN - 1549-3296
DOI - 10.1002/jbm.a.34905
Subject(s) - polyethylenimine , gene delivery , transfection , materials science , ethylene glycol , peg ratio , genetic enhancement , spermine , cytotoxicity , microbiology and biotechnology , biophysics , nuclear chemistry , cancer research , chemistry , biology , biochemistry , in vitro , organic chemistry , gene , finance , economics , enzyme
The clinical success of gene therapy critically depends upon the safety and efficiency of delivery system used. Although polyethylenimine (PEI) has been commonly used as an efficient cationic polymeric gene carrier due to its high transfection efficiency, its cytotoxicity and nondegradability limit the polymer's therapeutic applications in clinical trials. In this study, biocompatible polyspermine based on spermine (SPE) and poly(ethylene glycol) (PEG) diacrylate (SPE‐ alt ‐PEG) was synthesized using a Michael‐type addition reaction, and its ability as an alternative gene carrier for lung cancer therapy was evaluated. SPE‐ alt ‐PEG polyspermine was complexed with plasmid DNA, and the resulting complexes were characterized by particle size and surface charge by dynamic light scattering, complex formation and DNA protection ability by gel retardation, and complex shape by energy‐filtering transmission electron microscopy. The SPE‐ alt ‐PEG copolymer showed low cytotoxicity, and SPE‐ alt ‐PEG/DNA complexes showed efficacious transfection efficiency compared with 25 kDa PEI (PEI 25K). Also SPE‐ alt ‐PEG/GFP complexes were efficiently transferred into the lungs after aerosol administration without toxicity, and delivery of Pdcd4 gene as a therapeutic gene with SPE‐ alt ‐PEG polyspermine greatly reduced tumor size as well as tumor numbers in K‐ ras LA1 lung cancer model mice compared relative to the effect observed for PEI 25K. These results suggest that SPE‐ alt ‐PEG has potential as a gene carrier for lung cancer gene therapy. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 2230–2237, 2014.