【摘要】 肝癌致死率高、预后差,已成为人类健康的重大威胁.随着核酸生物技术的发展,核酸药物在肝癌治疗领域逐渐显示出巨大的应用潜力.核酸药物特异性强,潜在作用靶点丰富,研发周期相对较短,但核酸分子稳定性差,难以进入细胞,且无法逃逸溶酶体,转染效果差,因而核酸药物的应用离不开递送体系的开发.核酸药物递送体系包括病毒载体与非病毒载体,非病毒载体包括共价连接体系、无机纳米颗粒、脂质纳米颗粒(LNP)、聚合物纳米颗粒(PNP)和DNA纳米颗粒等.本文总结了面向肝癌的基因治疗策略,并系统性综述了各种递送手段的特点、适用场景及研究进展,为新型肝癌核酸药物递送体系的研究与开发提供了借鉴和参考.更多还原

【Abstract】 Liver cancer has become a major threat to human health due to its high lethality, poor prognosis and strong drug resistance. With the in-depth researches on liver cancer and the development of nucleic acid biotechnology, nucleic acid drugs have gradually shown great potential in liver cancer treatment. Compared with traditional therapeutic drugs like chemical drugs, nucleic acid drugs have the characteristics of strong specificity, rich potential targets, relatively short development cycle, and negligible toxic side effects, etc. However, due to the poor stability of nucleic acid molecules, it is difficult to achieve long circulation time in body, high internalization activity, and lysosomal escape capacity in cell, which leads to the low transfection efficiency and prevents it from exerting the therapeutic effect. Therefore, it’s of great importance to develop drug delivery systems for nucleic acid drugs to improve the therapeutic effect and enhance the stability as well as the targeting of nucleic acid drugs in vivo. Currently, the delivery vectors for nucleic acid drugs include viral vectors and non-viral vectors. Viral vectors, including adenovirus, lentivirus, etc., have the advantages of high transfection efficiency and high specificity, but their application prospect is greatly restricted due to the safety and ethical issues. Non-viral vectors are safer,more stable and structurally tunable compared with viral vectors. Non-viral vectors, including covalently attached systems,inorganic nanoparticles, lipid nanoparticles(LNP), polymer nanoparticles(PNP), DNA nanoparticles etc., have high application prospects due to their rich types, diverse and adjustable structures, and good biocompatibility. In this paper, we systematically summarize the current nucleic acid drug delivery systems, especially for liver cancer, and carefully classify the application scenarios and characteristics of the current delivery systems and introduce all the delivery systems as exhaustively as possible. It provides reference for the research and development of innovative nucleic acid drug delivery systems tailored for liver cancer. Collectively, we think that drug delivery systems for nucleic acid drugs could be potential in clinic to promote the improvement of liver cancer therapy.更多还原