Biologically responsive carrier-mediated anti-angiogenesis shRNA delivery for tumor treatment.
Biologically responsive carrier-mediated anti-angiogenesis shRNA delivery for tumor treatment.
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用于肿瘤治疗的生物响应性载体介导的抗血管生成 shRNA 递送
DOI：
10.1038/srep35661
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发表时间：
2016-10-19
影响因子：
4.6
通讯作者：
Yuan W
中科院分区：
文献类型：
--
作者：
Che J;Tao A;Chen S;Li X;Zhao Y;Yuan W
小分子干扰RNA（siRNA）为基因相关疾病的高效治疗带来了希望。然而，治疗性核酸的稳定和有效递送是RNA干扰疗法成功临床转化的先决条件。为了实现这一点，我们将低分子量聚乙烯亚胺（PEI，Mw < 2000）与2，6-吡啶二甲醛（PDA）缩合以合成生物响应性和可降解的阳离子聚合物（缩写为PDAPEI），其用作用于递送VEGF-A shRNA表达质粒DNA（pDNA）的基因载体。PDAPEI和pDNA之间的静电相互作用导致具有合适粒径和稳定zeta电位的纳米级聚合物的自组装。PDAPEI/pDNA复合物在30 w/w比率下表现出出色的基因转染和沉默效率，以及可忽略的细胞毒性。此外，所设计的聚合物对先天免疫系统没有刺激。此外，与PEI 25 KDa相比，聚合物实现了相对更好的抗血管生成功效，这导致皮下肿瘤小鼠模型中肿瘤生长的抑制。因此，PDAPEI有望成为肿瘤基因治疗的载体。
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.
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影响因子：
10.8
作者：
Pouton, CW;Lucas, P;Moss, SH
通讯作者：
Moss, SH
影响因子：
9.2
作者：
Gupta, Subash C.;Kim, Ji Hye;Prasad, Sahdeo;Aggarwal, Bharat B.
通讯作者：
Aggarwal, Bharat B.
双氨基甲酸酯交联低分子量聚乙烯亚胺聚阳离子作为癌症治疗的有效细胞内递送货物
影响因子：
10.2
作者：
Ge X;Feng J;Chen S;Zhang C;Ouyang Y;Liu Z;Yuan W
通讯作者：
Yuan W
影响因子：
3.5
作者：
Carmeliet, P
通讯作者：
Carmeliet, P
影响因子：
10.8
作者：
Kunath, K;von Harpe, A;Kissel, T
通讯作者：
Kissel, T