This study reports the development and pre-clinical evaluation of biodrug using RNA interference and nanotechnology. The major challenges in achieving targeted gene silencing in vivo include the stability of RNA molecules, accumulation into pharmacological levels, and site-specific targeting of the tumor. We report the use of Inulin for coating the arginine stabilized manganese oxide nanocuboids (MNCs) for oral delivery of shRNA to the gut. Furthermore, bio-distribution analysis exhibited site-specific targeting in the intestines, improved pharmacokinetic properties, and faster elimination from the system without cytotoxicity. To evaluate the therapeutic possibility and effectiveness of this multimodal bio-drug, it was orally delivered to Apc knockout colon cancer mice models. Persistent and efficient delivery of bio-drug was demonstrated by the knockdown of target genes and increased median survival in the treated cohorts. This promising utility of RNAi-Nanotechnology approach advocates the use of bio-drug in an effort to replace chemo-drugs as the future of cancer therapeutics.

本研究报告了使用 RNA 干扰和纳米技术的生物药物的开发和临床前评估。在体内实现靶向基因沉默的主要挑战包括 RNA 分子的稳定性、药理学水平的积累和肿瘤的位点特异性靶向。我们报告了使用菊粉来涂覆精氨酸稳定的氧化锰纳米立方体 (MNC)，以将 shRNA 口服递送至肠道。此外，生物分布分析显示出在肠道中的位点特异性靶向、改进的药代动力学特性以及更快地从系统中消除而没有细胞毒性。为了评估这种多模式生物药物的治疗可能性和有效性，将其口服递送至 Apc 基因敲除结肠癌小鼠模型。靶基因的敲低和治疗组中位生存期的增加证明了生物药物的持续有效递送。