Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
J Control Release. 2010 Apr 19;143(2):215-21. doi: 10.1016/j.jconrel.2009.11.015. Epub 2009 Nov 26.
The possibility of using genes as medicines to treat cancer is limited by the lack of safe and efficacious delivery systems able to deliver therapeutic genes selectively to tumors by intravenous administration. We investigate if the conjugation of the polypropylenimine dendrimer to transferrin, whose receptors are overexpressed on numerous cancers, could result in a selective gene delivery to tumors after intravenous administration, leading to an increased therapeutic efficacy. The objectives of this study are to evaluate the targeting and therapeutic efficacies of a novel transferrin-bearing polypropylenimine dendrimer. The intravenous administration of transferrin-bearing polypropylenimine polyplex resulted in gene expression mainly in the tumors. Consequently, the intravenous administration of the delivery system complexed to a therapeutic DNA led to a rapid and sustained tumor regression over one month, with long-term survival of 100% of the animals (90% complete response, 10% partial response).The treatment was well tolerated by the animals, with no apparent signs of toxicity. Transferrin-bearing polypropylenimine may thus be a promising gene delivery system for cancer therapy.
将基因作为药物治疗癌症的可能性受到限制，因为缺乏安全有效的输送系统，无法通过静脉注射将治疗基因选择性地递送到肿瘤。我们研究了将多聚体树枝状聚合物与转铁蛋白连接，因为许多癌症过度表达转铁蛋白受体，这是否会导致静脉注射后肿瘤的选择性基因传递，从而提高治疗效果。本研究的目的是评估新型转铁蛋白结合多聚体树枝状聚合物的靶向和治疗效果。静脉注射转铁蛋白结合多聚体树枝状聚合物多聚物导致基因表达主要在肿瘤中。因此，静脉注射该递送系统与治疗性 DNA 复合后，在一个月内导致肿瘤快速而持续的消退，动物的长期存活率为 100%（90%完全缓解，10%部分缓解）。该治疗方法被动物很好地耐受，没有明显的毒性迹象。因此，转铁蛋白结合多聚体树枝状聚合物可能是癌症治疗有前途的基因递送系统。
