title: Selective stimulation of caveolae-mediated endocytosis by an osmotic polymannitol-based gene transporter.
abstract: Controlling the cellular uptake mechanism and consequent intracellular route of polyplexes is important to improve the transfection efficiency of the non-viral gene delivery. Here, we report a new non-viral vector, polymannitol-based gene transporter (PMT), generated by crosslinking low molecular weight polyethylenimine with mannitol diacrylate, which has low cytotoxicity and good transfection efficiency. Interestingly, the uptake pathway of PMT/DNA complexes was shifted into caveolae-mediated endocytosis, avoiding lysosomal degradation. The mechanism of increased caveolae-mediated endocytosis of PMT/DNA complexes was found to be correlated with mechanosensing signal transduction by the hyperosmotic polymannitol part. Our results suggested that PMT, polymannitol-based gene transporter, is a safe and efficient gene delivery system with a well-modulated uptake pathway and intracellular route for gene therapy.
authors: Department of Agricultural Biotechnology, Seoul National University, Seoul, Korea.
authors: Tae-Eun
authors: TE
authors: Park
authors: Bitna
authors: B
authors: Kang
authors: You-Kyoung
authors: YK
authors: Kim
authors: Qiankun
authors: Q
authors: Zhang
authors: Won-Seok
authors: WS
authors: Lee
authors: Mohammad Ariful
authors: MA
authors: Islam
authors: Sang-Kee
authors: SK
authors: Kang
authors: Myung-Haing
authors: MH
authors: Cho
authors: Yun-Jaie
authors: YJ
authors: Choi
authors: Chong-Su
authors: CS
authors: Cho
mesh_terms: D021941:Caveolae / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D004705:Endocytosis; D005782:Gels; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D008353:Mannitol / Q000737:chemistry*; D008956:Models, Chemical; D009995:Osmosis; D010316:Particle Size; D011094:Polyethyleneimine / Q000737:chemistry; D015398:Signal Transduction
chemical_list: D005782:Gels; D018942:Macrolides; D008353:Mannitol; C040929:bafilomycin A1; D011094:Polyethyleneimine