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首页> 外文期刊>Biotechnology Progress >Cholesterol-conjugated PEGylated PAMAM as an efficient nanocarrier for plasmid encoding interleukin-12 immunogene delivery toward colon cancer cells
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Cholesterol-conjugated PEGylated PAMAM as an efficient nanocarrier for plasmid encoding interleukin-12 immunogene delivery toward colon cancer cells

机译：胆固醇缀合的聚乙二醇化帕姆作为用于编码白细胞介素-12免疫基因递送朝向结肠癌细胞的高效纳米载体

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摘要

IL-12 is a pleiotropic cytokine, which shows an ideal applicant for tumor immunotherapy, because of its features of creating an interconnection between innate (NK cells) and adaptive (cytotoxic T lymphocyte) immunity. IL-12 gene therapy is a useful technique to deliver an immune-modulatory gene directly into tumor site thereby limiting the adverse effects of systemic administration of IL-12 proteins. One of the most largely investigated non-viral gene carriers is polyamidoamine (PAMAM). In the current research, 5 and 3% of PAMAM primary amines were substituted to transmit the plasmid encoding IL-12 gene to cells by cholesteryl chloroformate and alkyl-PEG, respectively. The features of modified PAMAMs containing size and surface charge density, cytotoxicity, and transfection efficiency were investigated in colon cancer cells. in vitro experiment showed that this modified carrier with average size of about 160 nm and zeta potential of 30 mV was able to increase the level of IL-12 production up to two folds as compared to that of the unmodified PAMAM. Improvement of the polymer hydrophobic balance along with of the modulation of the surface positive charge could provide an efficient and safe non-viral IL-12 gene for colon cancer immunogene therapy.
机译：IL-12是一种肺炎细胞因子，其显示肿瘤免疫疗法的理想申请人，因为它的特征是在先天（NK细胞）和适应性（细胞毒性T淋巴细胞）免疫之间产生互连。 IL-12基因治疗是将免疫调节基因直接递送到肿瘤部位的有用技术，从而限制了IL-12蛋白的全身施用的不利影响。最大程度地研究的非病毒基因载体之一是聚酰胺胺（PAMAM）。在目前的研究中，5和3％的PAMAM伯胺被取代，分别通过胆固醇氯甲酸酯和烷基-PEG将编码IL-12基因的质粒传递给细胞。在结肠癌细胞中研究了含有尺寸和表面电荷密度，细胞毒性和转染效率的改进的PAMAM的特征。体外实验表明，与未修饰的PAMAM相比，该改性载体具有约160nm和30mM的Zeta电位的Zeta电位，其能够将IL-12的产量增加到两倍。随着表面阳性电荷的调节，聚合物疏水平衡的改善可以提供用于结肠癌免疫原序的有效和安全的非病毒IL-12基因。

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