Che Junyi, Tao Anqi, Chen Shun, Li Xiaoming, Zhao Yi, Yuan Weien
School of Pharmacy, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Sci Rep. 2016 Oct 19;6:35661. doi: 10.1038/srep35661.
Small interfering RNA (siRNA) has increased the hope for highly-efficient treatment of gene-related diseases. However, the stable and efficient delivery of therapeutic nucleic acids is a prerequisite for the successful clinical translation of RNA interfering therapy. To achieve this, we condensed the low molecular weight polyethyleneimine (PEI, Mw < 2000) with 2,6-pyridinedicarboxaldehyde (PDA) to synthesize a biologically responsive and degradable cationic polymer (abbreviated to PDAPEI) which was utilized as a gene vector for the delivery of a VEGF-A shRNA expression plasmid DNA (pDNA). The resulting electrostatic interaction between PDAPEI and pDNA led to the self-assembly of nanoscale polyplexes with suitable particle size and stable zeta potential. The PDAPEI/pDNA polyplexes demonstrated an outstanding gene transfection and silencing efficiency at 30 w/w ratio, as well as negligible cytotoxicity. Also, the designed polymer showed no stimulation to the innate immune system. Moreover, compared with PEI 25 KDa, the polyplexes accomplished comparatively better anti-angiogenesis efficacy, which resulted in the inhibition of tumor growth in subcutaneous tumor mice models. In conclusion, PDAPEI has great potential to be a gene delivery vector for cancer therapy.
小分子干扰RNA（siRNA）为高效治疗基因相关疾病带来了新希望。然而，治疗性核酸的稳定高效递送是RNA干扰疗法成功实现临床转化的前提条件。为实现这一目标，我们将低分子量聚乙烯亚胺（PEI，Mw < 2000）与2,6 - 吡啶二甲醛（PDA）缩合，合成了一种具有生物响应性和可降解性的阳离子聚合物（简称为PDAPEI），并将其用作基因载体来递送VEGF - A短发夹RNA表达质粒DNA（pDNA）。PDAPEI与pDNA之间产生的静电相互作用导致纳米级多聚体自组装形成具有合适粒径和稳定ζ电位的结构。PDAPEI/pDNA多聚体在30 w/w比例下表现出出色的基因转染和沉默效率，且细胞毒性可忽略不计。此外，所设计的聚合物对先天免疫系统无刺激作用。而且，与25 kDa的PEI相比，该多聚体在皮下肿瘤小鼠模型中实现了相对更好的抗血管生成效果，从而抑制了肿瘤生长。总之，PDAPEI作为癌症治疗的基因递送载体具有巨大潜力。
