title: MicroRNA delivery with osmotic polysorbitol-based transporter suppresses breast cancer cell proliferation.
abstract: MicroRNAs (miRNA) are short oligonucleotides of endogenous origin involved in post-transcriptional regulation and are altered in disease, making them potential therapeutic targets. miRNA replacement is necessary in cells with downregulated miRNAs levels in response to disease. miRNA 145 is a novel tumor suppressor gene involved in cell suppression, invasion and migration of cancer cells; it is downregulated in most cancers. Delivery of therapeutic miRNA using nanoparticles enhances the chances of successful delivery and expression of genes at the target site. We evaluated polysorbitol-mediated transporter (PSMT) in the cellular delivery of miRNA 145. The polysorbitol backbone possesses osmotic properties and leads to enhanced cellular uptake. PSMT delivers genes into cells by a caveolae-mediated endocytic pathway. Caveolae expression is usually altered in transformed cancer cells. Physicochemical characterization, and the transfection efficiency and transgene expression capability of PSMT/reporter plasmid DNA nanoparticles, were determined. GFP-tagged miRNA 145 delivery with PSMT was confirmed by confocal microscopy and Western blotting. The functional effects of miRNA 145 delivered with PSMT were analyzed by confocal microscopy, as well as in apoptosis, proliferation and wound healing assays. Finally, the expression of an miRNA 145 target protein, c-myc, was determined by Western blotting after intracellular delivery of PSMT/miRNA 145 nanoparticle (NP).
authors.affiliation: Department of Biomedical Science and 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; Brigham and Women's Hospital & Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Mohammad Ariful
authors.initials: MA
authors.lastname: Islam
authors.affiliation: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: Hwa-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Biomedical Science and BK21 PLUS Center for Creative Biomedical Scientists at Chonnam National University, Chonnam National University Medical School, Gwangju 501-746, South Korea.
authors.forename: Myoeng-Ju
authors.initials: MJ
authors.lastname: Moon
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: Department of Biomedical Science and 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
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D004247:DNA / Q000378:metabolism; D005260:Female; D018014:Gene Transfer Techniques; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011091:Polyesters / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D014162:Transfection; D019076:Transgenes
chemical_list: C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D011091:Polyesters; C569756:polysorbitol-based osmotically active transporter polymer; D011094:Polyethyleneimine; D004247:DNA
keywords: Breast cancer; MicroRNA 145; Nanoparticle; PSMT; Tumor suppression