Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Am J Cancer Res. 2011 Sep 1;1(1):25-42.
While small interfering RNA (siRNA) and microRNA (miRNA) have attracted extensive attention and showed significant promise for the study, diagnosis and treatment of human cancers, delivering siRNA or miRNA specifically and efficiently into tumor cells in vivo remains a great challenge. Delivery barriers, which arise mainly from the routes of administration associated with complex physiochemical microenvironments of the human body and the unique properties of RNAs, hinder the development of RNA-interference (RNAi)-based therapeutics in clinical practice. However, in available delivery systems, non-viral nanoparticle-based gene/RNA-delivery vectors, or nanovectors, are showing powerful delivery capacities and huge potential for improvements in functional nanomaterials, including novel fabrication approaches which would greatly enhance delivery performance. In this review, we summarize the currently recognized RNAi delivery barriers and the anti-barrier requirements related to vectors' properties. Recent efforts and achievements in the development of novel nanomaterials, nanovectors fabrication methods, and delivery approaches are discussed. We also review the outstanding needs in the areas of material synthesis and assembly, multifunction combinations, proper delivery and assisting approaches that require more intensive investigation for the comprehensive and effective delivery of RNAi by non-viral nanovectors.
虽然小干扰 RNA(siRNA)和 microRNA(miRNA)在人类癌症的研究、诊断和治疗方面引起了广泛关注,并显示出巨大的潜力,但将 siRNA 或 miRNA 特异性和有效地递送到体内肿瘤细胞仍然是一个巨大的挑战。递药障碍主要源于与人体复杂的物理化学微环境和 RNA 独特性质相关的给药途径,这阻碍了基于 RNA 干扰(RNAi)的治疗在临床实践中的发展。然而,在现有的递药系统中,基于非病毒纳米颗粒的基因/RNA 递药载体,或纳米载体,表现出强大的递药能力和对功能纳米材料的巨大改进潜力,包括新的制造方法,这将极大地提高递药性能。在这篇综述中,我们总结了目前公认的 RNAi 递药障碍以及与载体性质相关的抗障碍要求。讨论了新型纳米材料、纳米载体制造方法和递药方法的最新进展和成果。我们还回顾了在材料合成和组装、多功能组合、适当的递药和辅助方法方面的突出需求,这些需求需要更深入的研究,以实现非病毒纳米载体对 RNAi 的全面有效递药。