Abstract
High transfection efficiency and low cytotoxicity are the two key factors to be considered in the design of gene carriers. Herein, a novel and versatile gene carrier (PLL-RT) was prepared by introducing "molecular string" RT (i.e., p-toluylsulfonyl arginine) onto the polylysine backbone. The introduction of RT string contributed to the formation of multiple interactions between the polycationic gene carriers and cell membrane or DNA, as well as adopting α-helix conformation, all of which would be beneficial to enhance the gene transfection. In addition, RT string grafted onto other polycations such as hyperbranced PEI25k and dendrimer PAMAM could also acquire improved transfection efficiency and low cytotoxicity. Moreover, PLL-RT presented significant tumor inhibition effect in vivo. This work provided an effective strategy for constructing novel gene carriers with high transfection and low cytotoxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cardiolipins / metabolism
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Cell Line, Tumor
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Cell Survival / drug effects
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DNA / genetics*
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DNA / metabolism
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Endocytosis / physiology
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Endosomes / metabolism
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Female
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Gene Transfer Techniques*
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Humans
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Membranes, Artificial
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Mice, Inbred BALB C
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Molecular Conformation
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Neoplasms / therapy
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Particle Size
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Polylysine / analogs & derivatives*
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Polylysine / chemical synthesis
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Polylysine / metabolism
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Polylysine / toxicity
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RNA, Small Interfering / administration & dosage
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RNA, Small Interfering / genetics
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RNA, Small Interfering / metabolism
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RNA, Small Interfering / therapeutic use
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Tosylarginine Methyl Ester / analogs & derivatives*
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Tosylarginine Methyl Ester / chemical synthesis
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Tosylarginine Methyl Ester / metabolism
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Tosylarginine Methyl Ester / toxicity
Substances
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Cardiolipins
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Membranes, Artificial
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RNA, Small Interfering
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Polylysine
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DNA
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Tosylarginine Methyl Ester