Nanomedical Science, Yonsei University, Seoul, Republic of Korea.
Adv Drug Deliv Rev. 2012 Jun 1;64(8):720-9. doi: 10.1016/j.addr.2011.12.011. Epub 2011 Dec 24.
Oncolytic adenovirus (Ad) has been used in cancer gene therapy largely due to its ability to selectively infect and replicate in tumor cells. However, because the oncolytic antitumor activity is insufficient to effectively eliminate tumors, various strategies have been devised to improve the therapeutic efficacy. Single-vector Ads "armed" with short hairpin RNA, cytokines, or matrix-modulating proteins have been developed. Two clear advantages are viral amplification of the therapeutic gene, and the additive effects of oncolytic and therapeutic gene-mediated antitumor activities. To develop systemically injectable Ad carriers, strategies to modify the Ad surface with polymers, liposomes, or nanoparticles have been shown to extend circulation time, reduce immunogenicity, and result in increased antitumor effect as well as lower accumulation and toxicity in liver. Specific targeting platforms for tumor-selective oncolytic therapies against both primary and metastatic cancers have been developed. This review will focus on updated strategies to develop potent oncolytic Ads for use in cancer treatment.
溶瘤腺病毒（Ad）由于能够选择性地感染和复制肿瘤细胞，因此在癌症基因治疗中得到了广泛应用。然而，由于溶瘤抗肿瘤活性不足以有效消除肿瘤，因此设计了各种策略来提高治疗效果。已经开发了带有短发夹 RNA、细胞因子或基质调节蛋白的单载体 Ads。这有两个明显的优势，即治疗基因的病毒扩增，以及溶瘤和治疗基因介导的抗肿瘤活性的相加作用。为了开发全身性可注射的 Ad 载体，已经证明用聚合物、脂质体或纳米颗粒修饰 Ad 表面的策略可以延长循环时间、降低免疫原性，并导致抗肿瘤效果增加，以及在肝脏中的积累和毒性降低。已经开发了针对原发性和转移性癌症的肿瘤选择性溶瘤治疗的特异性靶向平台。这篇综述将重点介绍开发用于癌症治疗的有效溶瘤 Ads 的最新策略。
