Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Iran.
Tehran University of Medical Science, Otolaryngology Department, Tehran, Iran.
Environ Res. 2023 Dec 15;239(Pt 2):117263. doi: 10.1016/j.envres.2023.117263. Epub 2023 Oct 4.
RNA interference (RNAi) is a unique treatment approach used to decrease a disease's excessive gene expression, including cancer. SiRNAs may find and destroy homologous mRNA sequences within the cell thanks to RNAi processes. However, difficulties such poor cellular uptake, off-target effects, and susceptibility to destruction by serum nucleases in the bloodstream restrict the therapeutic potential of siRNAs. Since some years ago, siRNA-based therapies have been in the process of being translated into the clinic. Therefore, the primary emphasis of this work is on sophisticated nanocarriers that aid in the transport of siRNA payloads, their administration in combination with anticancer medications, and their use in the treatment of cancer. The research looks into molecular manifestations, difficulties with siRNA transport, the design and development of siRNA-based delivery methods, and the benefits and drawbacks of various nanocarriers. The trapping of siRNA in endosomes is a challenge for the majority of delivery methods, which affects the therapeutic effectiveness. Numerous techniques for siRNA release, including as pH-responsive release, membrane fusion, the proton sponge effect, and photochemical disruption, have been studied to overcome this problem. The present state of siRNA treatments in clinical trials is also looked at in order to give a thorough and systematic evaluation of siRNA-based medicines for efficient cancer therapy.
RNA 干扰 (RNAi) 是一种独特的治疗方法，用于降低疾病的过度基因表达，包括癌症。由于 RNAi 过程，siRNA 可以在细胞内发现并破坏同源的 mRNA 序列。然而，siRNA 的治疗潜力受到一些困难的限制，如细胞摄取能力差、脱靶效应和对血液中血清核酶的易感性。自数年前以来，基于 siRNA 的疗法一直在向临床转化。因此，这项工作的主要重点是开发复杂的纳米载体，以帮助输送 siRNA 有效载荷，将其与抗癌药物联合使用，并用于癌症治疗。该研究探讨了分子表现、siRNA 转运的困难、基于 siRNA 的递送方法的设计和开发，以及各种纳米载体的优缺点。大多数递送方法都存在将 siRNA 困在内涵体中的挑战，这会影响治疗效果。已经研究了许多用于 siRNA 释放的技术，包括 pH 响应性释放、膜融合、质子海绵效应和光化学破坏，以克服这个问题。还研究了临床试验中 siRNA 治疗的现状，以便对基于 siRNA 的药物进行全面和系统的评估，以实现有效的癌症治疗。
