Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, 12850 Montview Boulevard, Aurora, Colorado 80045, USA.
J Control Release. 2013 Dec 28;172(3):730-6. doi: 10.1016/j.jconrel.2013.08.300. Epub 2013 Sep 11.
The objective of a systemically administered cancer gene therapy is to achieve gene expression that is isolated to the tumor tissue. Unfortunately, viral systems have strong affinity for the liver, and delivery from non-viral cationic systems often results in high expression in the lungs. Non-specific delivery to these organs must be overcome if tumors are to be aggressively treated with genes such as IL-12 which activates a tumor immune response, and TNF-alpha which can induce tumor cell apoptosis. Techniques which have led to specific expression in tumor tissue include receptor targeting through ligand conjugation, utilization of tumor specific promoters and viral mutation in order to take advantage of proteins overexpressed in tumor cells. This review analyzes these techniques applied to liposomal, PEI, dendrimer, stem cell and viral gene delivery systems in order to determine the techniques that are most effective in achieving tumor specific gene expression after systemic administration.
系统给药的癌症基因治疗的目的是实现仅在肿瘤组织中表达的基因。不幸的是，病毒系统对肝脏具有很强的亲和力，而非病毒阳离子系统的传递往往会导致肺部的高表达。如果要使用白细胞介素 12 (IL-12)等基因积极治疗肿瘤，这些基因可以激活肿瘤免疫反应，肿瘤坏死因子-α (TNF-α)可以诱导肿瘤细胞凋亡，就必须克服向这些器官的非特异性传递。通过配体缀合进行受体靶向、利用肿瘤特异性启动子和病毒突变以利用肿瘤细胞中过度表达的蛋白等技术，可导致在肿瘤组织中特异性表达。本综述分析了这些技术在脂质体、PEI、树枝状聚合物、干细胞和病毒基因传递系统中的应用，以确定在系统给药后实现肿瘤特异性基因表达最有效的技术。
