title: Selective transfection with osmotically active sorbitol modified PEI nanoparticles for enhanced anti-cancer gene therapy.
abstract: Polysorbitol-mediated transporter (PSMT) has been previously shown to achieve high transfection efficiency with minimal cytotoxicity. Polysorbitol backbone possesses osmotic properties and leads to enhanced cellular uptake. The PSMT/pDNA nanoparticles were prepared and the particle size, surface charge of the nanoparticles was determined for the study. PSMT delivers genes into cells by the caveolae mediated endocytic pathway. Caveolae expression is usually altered in transformed cancer cells. Transfection through the caveolae may help PSMT to selectively transfect cancer cells rather than normal cells. Transfection of the luciferase gene by PSMT was tested in various cell types including cancer cell lines, primary cells, and immortalized cells. Luciferase transgene expression mediated by PSMT was remarkably increased in HeLa cells compared to expression using the control carrier Lipofectamine. Moreover, the toxicity of PSMT was comparable to the control carrier (Lipofectamine) in the same cells. Selective transfection of cancer cells using PSMT was further confirmed by co-culture of cancer and normal cells, which showed that transgene expression was pre-dominantly achieved in cancer cells. A functional p53 gene was also delivered into HeLa cells using PSMT and the selective transgene expression of p53 protein in cancer cells was analyzed through western blotting and confocal microscopy. HeLa cells transfected with PSMT/p53 plasmid nanoparticles showed cellular damage and apoptosis, which was confirmed through propidium iodide staining.
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju 501-746, South Korea; BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: Kim Cuc Thi
authors.initials: KC
authors.lastname: Nguyen
authors.affiliation: Department of Biomedical Science and Chonnam National University Medical School, Gwangju 501-746, South Korea; BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: Muthunarayanan
authors.initials: M
authors.lastname: Muthiah
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Department of Biomedical Science and Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: R Santhosh
authors.initials: RS
authors.lastname: Kalash
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
authors.forename: Chong-Su
authors.initials: CS
authors.lastname: Cho
authors.affiliation: School of Integrative Engineering, Chung-Ang University, Dongjak-gu, Seoul 156-756, South Korea.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Park
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, South Korea.
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Lee
authors.affiliation: Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Jeollanamdo 519-763, South Korea.
authors.forename: Hyeoung-Joon
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Chonnam National University Medical School, Gwangju 501-746, South Korea; BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea. Electronic address: pik96@chonnam.ac.kr.
authors.forename: In-Kyu
authors.initials: IK
authors.lastname: Park
authors.affiliation: Department of Biochemistry, Chonnam National University Medical School, Gwangju 501-746, South Korea; BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea. Electronic address: kacho@chonnam.ac.kr.
authors.forename: Kyung A
authors.initials: KA
authors.lastname: Cho
mesh_terms: D000818:Animals; D017209:Apoptosis; D021941:Caveolae / Q000378:metabolism; D045744:Cell Line, Tumor; D004705:Endocytosis; D015870:Gene Expression; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010957:Plasmids / Q000378:metabolism*; D011091:Polyesters / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D061251:Primary Cell Culture; D055672:Static Electricity; D019076:Transgenes; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D008055:Lipids; C086724:Lipofectamine; D011091:Polyesters; D016159:Tumor Suppressor Protein p53; C569756:polysorbitol-based osmotically active transporter polymer; D011094:Polyethyleneimine; D008156:Luciferases
keywords: Caveolae-dependent endocytosis; Polyethylenimine; Sorbitol; Transfection efficiency