Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Pilani Campus, Vidya Vihar, Pilani - 333 031, Rajasthan, India.
Mol Pharm. 2020 Nov 2;17(11):4040-4066. doi: 10.1021/acs.molpharmaceut.0c00709. Epub 2020 Oct 2.
Nucleic acid therapeutics for RNA interference (RNAi) are gaining attention in the treatment and management of several kinds of the so-called "undruggable" tumors via targeting specific molecular pathways or oncogenes. Synthetic ribonucleic acid (RNAs) oligonucleotides like siRNA, miRNA, shRNA, and lncRNA have shown potential as novel therapeutics. However, the delivery of such oligonucleotides is significantly hampered by their physiochemical (such as hydrophilicity, negative charge, and instability) and biopharmaceutical features ( serum stability, fast renal clearance, interaction with extracellular proteins, and hindrance in cellular internalization) that markedly reduce their biological activity. Recently, several nanocarriers have evolved as suitable non-viral vectors for oligonucleotide delivery, which are known to either complex or conjugate with these oligonucleotides efficiently and also overcome the extracellular and intracellular barriers, thereby allowing access to the tumoral micro-environment for the better and desired outcome in glioblastoma multiforme (GBM). This Review focuses on the up-to-date advancements in the field of RNAi nanotherapeutics utilized for GBM treatment.
核酸疗法中的 RNA 干扰(RNAi)正在通过靶向特定的分子途径或癌基因,引起人们对治疗和管理几种所谓的“不可用药”肿瘤的关注。合成的核糖核酸(RNAs)寡核苷酸,如 siRNA、miRNA、shRNA 和 lncRNA,已显示出作为新型治疗药物的潜力。然而,这些寡核苷酸的传递受到其物理化学性质(如亲水性、负电荷和不稳定性)和生物制药特性(血清稳定性、快速肾清除、与细胞外蛋白的相互作用以及细胞内化的阻碍)的严重阻碍,这些特性显著降低了它们的生物活性。最近,几种纳米载体已演变为适用于寡核苷酸递送的非病毒载体,这些载体被认为可以有效地与这些寡核苷酸进行复合或缀合,并且还可以克服细胞外和细胞内的障碍,从而使肿瘤微环境能够更好地进入,从而在多形性胶质母细胞瘤(GBM)中获得更好的预期效果。这篇综述重点介绍了用于治疗 GBM 的 RNAi 纳米治疗学领域的最新进展。