Attia Mohamed S, Kijanka Gregor, Nguyen Nam-Trung, Zhang Jun, An Hongjie
Queensland Micro and Nanotechnology Centre, Griffith University, Nathan, QLD 4111, Australia.
Acta Pharm Sin B. 2025 Jan;15(1):52-96. doi: 10.1016/j.apsb.2024.09.009. Epub 2024 Sep 14.
Modern oncology is rapidly evolving, driven by recent advances in RNA-based therapeutics. As new emerging cutting-edge technology, mRNA vaccines hold excellent promise for encoding immunostimulatory molecules, tumor-associated antigens, neoantigens, and chimeric antigen receptors for T-cell reprogramming. RNA interference tools enable highly effective post-transcriptional gene silencing that has rapidly progressed towards more tailored antitumor treatments targeting key molecular players in tumor progression and drug resistance. The inherent challenges and limitations of RNA-based tools, such as size, low stability and surface charges hindering direct cell entry, along with the short circulatory half-life and rapid clearance, call for new and improved RNA delivery systems enabling enhanced gene delivery. Nanoplatforms, particularly certain types of lipid, polymeric nanoparticles and inorganic nanoparticles, provide designed means to address the challenges of RNA delivery and cellular uptake. This paper explores the challenges and barriers while giving insight into the future perspective of RNA-based cancer therapeutics in the context of delivery nanoplatforms and the challenges during development.
在基于RNA的治疗方法取得最新进展的推动下，现代肿瘤学正在迅速发展。作为新兴的前沿技术，mRNA疫苗在编码免疫刺激分子、肿瘤相关抗原、新抗原以及用于T细胞重编程的嵌合抗原受体方面具有巨大潜力。RNA干扰工具能够实现高效的转录后基因沉默，并且已经迅速朝着针对肿瘤进展和耐药性的关键分子靶点进行更具针对性的抗肿瘤治疗发展。基于RNA的工具存在一些固有的挑战和局限性，例如尺寸、稳定性低以及表面电荷阻碍直接进入细胞，同时循环半衰期短且清除迅速，这就需要新的、经过改进的RNA递送系统来增强基因递送。纳米平台，特别是某些类型的脂质、聚合物纳米颗粒和无机纳米颗粒，为解决RNA递送和细胞摄取的挑战提供了设计手段。本文探讨了这些挑战和障碍，同时深入了解了在递送纳米平台背景下基于RNA的癌症治疗方法的未来前景以及开发过程中面临的挑战。
