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 mol...

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Bibliographic Details
Published inBiomaterials Vol. 33; no. 29; pp. 7272 - 7281
Main Authors Park, Tae-Eun, Kang, Bitna, Kim, You-Kyoung, Zhang, Qiankun, Lee, Won-Seok, Islam, Mohammad Ariful, Kang, Sang-Kee, Cho, Myung-Haing, Choi, Yun-Jaie, Cho, Chong-Su
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.10.2012
Subjects
Advanced Basic Science
Caveolae - metabolism
Caveolae-mediated endocytosis
Cell Line, Tumor
Cell Survival
Dentistry
Endocytosis
Gels
Gene delivery
Gene Transfer Techniques
Genetic Therapy - methods
Genetic Vectors
HeLa Cells
Humans
Hyperosmotic stress
Macrolides - pharmacology
Mannitol - chemistry
Models, Chemical
Osmosis
Particle Size
Polyethyleneimine - chemistry
Polyethylenimine
Polymannitol
Signal Transduction
Gene delivery
Polyethylenimine
Polymannitol
Caveolae-mediated endocytosis
Hyperosmotic stress
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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2012.06.037