文章：

利用一种新型PEI复合体的辐射增强质粒DNA传递到肿瘤

Radiation-enhanced delivery of plasmid DNA to tumors utilizing a novel PEI polyplex 

原文发布日期：2017-12-19 

英文摘要：

The excitement surrounding the potential of gene therapy has been tempered due to the challenges that have thus far limited its successful implementation in the clinic such as issues regarding stability, transfection efficiency, and toxicity. In this study, low molecular weight linear polyethyleneimine (2.5 kDa) was modified by conjugation to a lipid, lithocholic acid, and complexed with a natural polysaccharide, dermatan sulfate (DS), to mask extra cationic charges of the modified polymer. In vitro examination revealed that these modifications improved complex stability with plasmid DNA (pDNA) and transfection efficiency. This novel ternary polyplex (pDNA/3E/DS) was used to investigate if tumor-targeted radiotherapy led to enhanced accumulation and retention of gene therapy vectors in vivo in tumor-bearing mice. Imaging of biodistribution revealed that tumor irradiation led to increased accumulation and retention as well as decreased off-target tissue buildup of pDNA in not only pDNA/3E/DS, but also in associated PEI-based polyplexes and commercial DNA delivery vehicles. The DS-containing complexes developed in this study displayed the greatest increase in tumor-specific pDNA delivery. These findings demonstrate a step forward in nucleic acid vehicle design as well as a promising approach to overall cancer gene therapy through utilization of radiotherapy as a tool for enhanced delivery. 

摘要翻译： 

尽管基因治疗的潜力令人振奋，但稳定性、转染效率和毒性等问题迄今仍限制其在临床中的成功应用。本研究通过将低分子量线性聚乙烯亚胺（2.5 kDa）与脂质石胆酸共价结合，并与天然多糖硫酸皮肤素（DS）复合，以屏蔽修饰后聚合物多余的阳离子电荷。体外实验表明，这些修饰提高了复合物与质粒DNA（pDNA）的稳定性及转染效率。采用这种新型三元复合物（pDNA/3E/DS）探究肿瘤靶向放疗是否能够增强基因治疗载体在荷瘤小鼠体内的聚集与滞留。生物分布成像显示：不仅pDNA/3E/DS组，包括相关PEI基复合物及商品化DNA递送载体在内的所有实验组中，肿瘤照射均能促进pDNA在靶组织的聚集与滞留，并减少脱靶组织沉积。其中含DS复合物在肿瘤特异性pDNA递送方面提升最为显著。这些发现不仅推动了核酸载体的设计创新，更为癌症基因治疗提供了新思路——通过放射治疗实现增强型基因递送策略。

原文链接：

Radiation-enhanced delivery of plasmid DNA to tumors utilizing a novel PEI polyplex