title: Endosomal pH responsive polymers for efficient cancer targeted gene therapy.
abstract: Treatment of human diseases at gene level is always limited by effective gene delivery vectors. In this study, we designed and developed an endosomal pH sensitive targeted gene delivery system, folic acid functionalized Schiff-base linked imidazole chitosan (FA-SLICS), for cancer therapy. The FA-SLICS is able to self-assemble plasmid DNA (pDNA) into nano-scaled polyplexes under a neutral condition and to release the loaded pDNA in the endosomal microenvironment due to the presence of pH sensitive Schiff-base moieties along chitosan backbones. The FA-SLICS has negligible cytotoxicity to normal cells (CHO), but displays slight toxicity to cancer cells (HeLa and HepG2). In addition, FA-SLICS can selectively and efficiently transfect FR (folate receptor) positive cells (HeLa cells) as a gene carrier. Therefore, the FA-SLICS should be a promising delivery vector in cancer gene therapy based on its cell targeting capability and intracellular microenvironment controlled delivery mechanism.
authors.affiliation: School of Chemical Engineering, The University of Adelaide, Adelaide 5005, SA, Australia.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Shi
authors.affiliation: School of Chemical Engineering, The University of Adelaide, Adelaide 5005, SA, Australia.
authors.forename: Hu
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Chemical Engineering, The University of Adelaide, Adelaide 5005, SA, Australia. Electronic address: jingxiu.bi@adelaide.edu.au.
authors.forename: Jingxiu
authors.initials: J
authors.lastname: Bi
authors.affiliation: School of Chemical Engineering, The University of Adelaide, Adelaide 5005, SA, Australia. Electronic address: s.dai@adelaide.edu.au.
authors.forename: Sheng
authors.initials: S
authors.lastname: Dai
mesh_terms: D000818:Animals; D001692:Biological Transport; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry; D003412:Cricetulus; D004339:Drug Compounding; D011992:Endosomes / Q000378:metabolism*; D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007093:Imidazoles / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism*; D012545:Schiff Bases / Q000737:chemistry*
chemical_list: D005456:Fluorescent Dyes; D058973:Folate Receptors, GPI-Anchored; D007093:Imidazoles; D008081:Liposomes; D012545:Schiff Bases; D048271:Chitosan; D005492:Folic Acid
keywords: Gene therapy; Schiff-base; Targeting delivery; pH sensitive