Meyer Martin, Wagner Ernst
Department of Pharmacy, Center of Drug Research, Pharmaceutical Biology-Biotechnology, Ludwig Maximilian University, Munich 81377, Germany.
Hum Gene Ther. 2006 Nov;17(11):1062-76. doi: 10.1089/hum.2006.17.1062.
Increased understanding of the molecular pathological mechanisms of cancer, the advent of novel molecular tools such as synthetic small interfering RNA (siRNA) or plasmid DNA-based vectors (pDNA), and technology for the in vivo delivery of such biomolecular therapeutics have provided an encouraging perspective for cancer therapy. Numerous pDNAs and siRNAs have been tested in preclinical cancer models, and these first approaches have reached clinical evaluation. The therapeutic effector mechanisms include interference with neoangiogenesis, blockage of cell division, promotion of apoptosis and sensitization to chemotherapy, delivery of cytotoxic genes, and activation of anticancer immune responses. Physical methods have been developed for highly effective regional delivery. A series of innovative "smart" formulations directs the current development toward safe and effective systemic tumor-targeted delivery of pDNA and siRNA.
对癌症分子病理机制的深入了解、诸如合成小干扰RNA（siRNA）或基于质粒DNA的载体（pDNA）等新型分子工具的出现，以及此类生物分子疗法的体内递送技术，为癌症治疗提供了令人鼓舞的前景。众多pDNA和siRNA已在临床前癌症模型中进行了测试，这些初步方法已进入临床评估阶段。治疗效应机制包括干扰新生血管生成、阻断细胞分裂、促进细胞凋亡以及对化疗的致敏作用、递送细胞毒性基因，以及激活抗癌免疫反应。已开发出用于高效区域递送的物理方法。一系列创新的“智能”制剂将当前的研发方向导向安全有效的pDNA和siRNA全身肿瘤靶向递送。
