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首页> 美国卫生研究院文献>International Journal of Nanomedicine >Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors
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Self-assembled supramolecular nano vesicles for safe and highly efficient gene delivery to solid tumors

机译：自组装的超分子纳米囊泡可将基因安全高效地递送至实体瘤

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The main obstacles for cationic polyplexes in gene delivery are in vivo instability and low solid-tumor accumulation. Safe vectors with high transfection efficiency and in vivo tumor accumulation are therefore highly desirable. In this study, the amphiphilic block copolymer poly(n-butyl methacrylate)-b-poly(N-acryloylmorpholine) was synthesized by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. The corresponding well-defined vesicles with narrow size distribution were tailored by finely regulating the packing parameter (β) of copolymer (1/2 < β < 1). Compared with traditional “gold-standard” polycation (polyethylenimine, 25 kDa), plasmid DNA condensing efficiency, DNase I degradation protection, and cellular uptake were improved by the supramolecular nano vesicles. In addition, the plasmid DNA transferring efficiency in 10% fetal bovine serum medium was enlarged five times to that of polyethylenimine in renal tubular epithelial and human hepatocellular carcinoma cell lines. This improved in vitro transfection was mainly attributed to the densely packed bilayer. This stealth polyplex showed high serum stability via entropic repulsion, which further protected the polyplex from being destroyed during sterilization. As indicated by the IVIS® Lumina II Imaging System (Caliper Life Sciences, Hopkinton, MA) 24 hours post-intravenous administration, intra-tumor accumulation of the stealth polyplex was clearly promoted. This study successfully circumvented the traditional dilemma of efficient gene transfection at a high nitrogen-from-polyethylenimine to phosphate-from-DNA ratio that is accompanied with site cytotoxicity and low stability. As such, these simply tailored noncytotoxic nano vesicles show significant potential for use in practical gene therapy.
机译：阳离子多聚体在基因传递中的主要障碍是体内不稳定性和低实体瘤积累。因此，非常需要具有高转染效率和体内肿瘤积累的安全载体。在这项研究中，两亲嵌段共聚物聚（甲基丙烯酸正丁酯）-b-聚（N-丙烯酰基吗啉）是通过可逆的加成-断裂链转移（RAFT）自由基聚合反应合成的。通过精细调节共聚物的填充参数（β）（1/2 <β<1），可以定制出具有窄尺寸分布的相应定义明确的囊泡。与传统的“金标准”聚阳离子（聚乙烯亚胺，25 kDa）相比，超分子纳米囊泡改善了质粒DNA的浓缩效率，DNase I降解保护和细胞摄取。此外，在肾小管上皮细胞和人肝癌细胞系中，质粒DNA在10％胎牛血清培养基中的转移效率是聚乙烯亚胺的5倍。这种改进的体外转染主要归因于紧密包装的双层。这种隐形复合物通过熵排斥显示出高的血清稳定性，这进一步保护了复合物在灭菌过程中不被破坏。如IVIS ® Lumina II成像系统（卡利珀生命科学，霍普金顿，马萨诸塞州）所示，在静脉给药后24小时，明显促进了隐形复合物的肿瘤内蓄积。这项研究成功地解决了传统的高效基因转染难题，即高氮-从-聚乙烯亚胺到磷酸-从-DNA的比率，同时具有站点细胞毒性和低稳定性。这样，这些简单定制的无细胞毒性的纳米囊泡在实际的基因治疗中显示出巨大的潜力。

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