Scarabel Lucia, Perrone Francesca, Garziera Marica, Farra Rossella, Grassi Mario, Musiani Francesco, Russo Spena Concetta, Salis Barbara, De Stefano Lucia, Toffoli Giuseppe, Rizzolio Flavio, Tonon Federica, Abrami Michela, Chiarappa Gianluca, Pozzato Gabriele, Forte Giancarlo, Grassi Gabriele, Dapas Barbara
a Experimental and Clinical Pharmacology Unit , C.R.O. National Cancer Institute , Aviano , Italy.
b Department of Life Sciences, Cattinara University Hospital , University of Trieste , Trieste , Italy.
Expert Opin Drug Deliv. 2017 Jun;14(6):797-810. doi: 10.1080/17425247.2017.1292247. Epub 2017 Feb 17.
hepatocellular carcinoma (hcc) is the predominant form of primary liver cancer and the second leading cause of cancer-associated mortality worldwide. available therapies for hcc have limited efficacy due to often late diagnosis and the general resistance of hcc to anti-cancer agents; therefore, the development of novel therapeutics is urgently required. small-interfering rna (sirna) molecules are short, double-stranded rnas that specifically recognize and bind the mrna of a target gene to inhibit gene expression. despite the great therapeutic potential of sirnas towards many human tumors including hcc, their use is limited by suboptimal delivery. Areas covered: In this review, we outline the current data regarding the therapeutic potential of siRNAs in HCC and describe the development of effective siRNA delivery systems. We detail the key problems associated with siRNA delivery and discuss the possible solutions. Finally, we provide examples of the various siRNA delivery strategies that have been employed in animal models of HCC and in human patients enrolled in clinical trials. Expert opinion: Despite the existing difficulties in siRNA delivery for HCC, the increasing scientific attention and breakthrough studies in this field is facilitating the design of novel and efficient technical solutions that may soon find practical applications.
肝细胞癌（HCC）是原发性肝癌的主要形式，也是全球癌症相关死亡的第二大原因。由于HCC往往诊断较晚且对抗癌药物普遍耐药，现有的HCC治疗方法疗效有限；因此，迫切需要开发新的治疗方法。小干扰RNA（siRNA）分子是短的双链RNA，可特异性识别并结合靶基因的mRNA以抑制基因表达。尽管siRNA对包括HCC在内的许多人类肿瘤具有巨大的治疗潜力，但其应用受到递送效果不佳的限制。涵盖领域：在本综述中，我们概述了关于siRNA在HCC中的治疗潜力的当前数据，并描述了有效的siRNA递送系统的发展。我们详细介绍了与siRNA递送相关的关键问题，并讨论了可能的解决方案。最后，我们提供了在HCC动物模型和参与临床试验的人类患者中采用的各种siRNA递送策略的实例。专家观点：尽管目前在HCC的siRNA递送方面存在困难，但该领域越来越多的科学关注和突破性研究正在促进新型高效技术解决方案的设计，这些解决方案可能很快会找到实际应用。
