Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection
Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection
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DOI：
10.1080/09205063.2015.1054922
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发表时间：
2015-05
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影响因子：
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通讯作者：
Kai Li;Hikari Sato;Chan Woo Kim;Yuta Nakamura;G. Zhao;Daiki Funamoto;T. Nobori;A. Kishimura;Takeshi Mori;Y. Katayama
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文献类型：
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作者：
Kai Li;Hikari Sato;Chan Woo Kim;Yuta Nakamura;G. Zhao;Daiki Funamoto;T. Nobori;A. Kishimura;Takeshi Mori;Y. Katayama
我们合成了以蛋白激酶Cα（PKCα）底物肽和正十五烷醇（正十五烷醇）修饰的多聚赖氨酸（PLL）为主链的多聚基因载体。由于接枝的底物肽，预期从这些载体制备的多聚物显示由细胞内PKCα磷酸化肽触发的基因表达。主链上的改性烷基硫醇通过二硫键交联和疏水性相互作用稳定了聚合物。发现当主链中的烷乙氧基化物含量足够低（PLL的ε-胺基的4-mol%-修饰）以使细胞毒性效应最小化时，多聚物显示出体外基因表达。即使烷醇的含量低，该复合物在模型血清溶液中具有显著的稳定性，并显示出更长的体内血液循环。静脉注射后，该复合物在肿瘤中明显积聚。
We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase Cα (PKCα) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKCα. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLL’s ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.