Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 161 Cathedral Street, Glasgow G4 0RE, United Kingdom.
Biomaterials. 2012 Mar;33(9):2701-9. doi: 10.1016/j.biomaterials.2011.12.019. Epub 2011 Dec 24.
The potential of gene therapy to treat cancer is hampered by the lack of safe and efficacious gene delivery systems able to selectively deliver therapeutic genes to tumors by intravenous administration. With the long-term aim of developing an efficacious cancer-targeted gene medicine, we demonstrated that transferrin-bearing polypropylenimine dendrimer complexed to a plasmid DNA encoding p73 led to an enhanced anti-proliferative activity in vitro, by up to 120-fold in A431 compared to the unmodified dendriplex. In vivo, the intravenous administration of this p73-encoding dendriplex resulted in a rapid and sustained inhibition of tumor growth over one month, with complete tumor suppression for 10% of A431 and B16-F10 tumors and long-term survival of the animals. The treatment was well tolerated by the animals, with no apparent signs of toxicity. These results suggest that the p73-encoding tumor-targeted polypropylenimine dendrimer should be further explored as a therapeutic strategy for cancer therapy.
基因治疗治疗癌症的潜力受到缺乏安全有效的基因传递系统的阻碍，这些系统能够通过静脉内给药选择性地将治疗基因递送到肿瘤。为了长期开发有效的癌症靶向基因药物，我们证明了转铁蛋白结合的多聚丙稀亚胺树枝状聚合物复合物与编码 p73 的质粒 DNA 结合，可使 A431 体外的增殖活性增强多达 120 倍，与未修饰的树枝状聚合物复合物相比。在体内，静脉内给予这种编码 p73 的树枝状聚合物复合物可在一个月内迅速和持续地抑制肿瘤生长，10%的 A431 和 B16-F10 肿瘤完全抑制，动物长期存活。该治疗方法被动物很好地耐受，没有明显的毒性迹象。这些结果表明，编码 p73 的肿瘤靶向多聚丙稀亚胺树枝状聚合物作为癌症治疗的治疗策略应进一步探索。
