Habib Saffiya, Singh Moganavelli
Nano-Gene and Drug Delivery Laboratory, Discipline of Biochemistry, School of Life Sciences, University of KwaZulu- Natal, Private Bag X54001, Durban, South Africa.
Pharm Nanotechnol. 2022;10(3):164-181. doi: 10.2174/2211738510666220606102906.
Nucleic acid-mediated therapy holds immense potential in treating recalcitrant human diseases such as cancer. This is underscored by advances in understanding the mechanisms of gene regulation. In particular, the endogenous protective mechanism of gene silencing known as RNA interference (RNAi) has been extensively exploited.
We review the developments from 2011 to 2021 using nano-graphene oxide, carbon nanotubes, fullerenes, carbon nanohorns, carbon nanodots and nanodiamonds for the delivery of therapeutic small RNA molecules.
Appropriately designed effector molecules such as small interfering RNA (siRNA) can, in theory, silence the expression of any disease-causing gene. Alternatively, siRNA can be generated in vivo by introducing plasmid-based short hairpin RNA (shRNA) expression vectors. Other small RNAs, such as micro RNA (miRNA), also function in post-transcriptional gene regulation and are aberrantly expressed under disease conditions. The miRNA-based therapy involves either restoration of miRNA function through the introduction of miRNA mimics; or the inhibition of miRNA function by delivering anti-miRNA oligomers. However, the large size, hydrophilicity, negative charge and nuclease-sensitivity of nucleic acids necessitate an appropriate carrier for their introduction as medicine into cells.
While numerous organic and inorganic materials have been investigated for this purpose, the perfect carrier agent remains elusive. Carbon-based nanomaterials have received widespread attention in biotechnology recently due to their tunable surface characteristics and mechanical, electrical, optical and chemical properties.
核酸介导的疗法在治疗癌症等顽固性人类疾病方面具有巨大潜力。对基因调控机制理解的进展突出了这一点。特别是，被称为RNA干扰（RNAi）的基因沉默内源性保护机制已被广泛利用。
我们回顾了2011年至2021年期间使用纳米氧化石墨烯、碳纳米管、富勒烯、碳纳米角、碳纳米点和纳米金刚石递送治疗性小RNA分子的进展。
理论上，适当设计的效应分子，如小干扰RNA（siRNA），可以沉默任何致病基因的表达。或者，可以通过引入基于质粒的短发夹RNA（shRNA）表达载体在体内产生siRNA。其他小RNA，如微小RNA（miRNA），也在转录后基因调控中发挥作用，并且在疾病条件下异常表达。基于miRNA的疗法包括通过引入miRNA模拟物恢复miRNA功能；或通过递送抗miRNA寡聚物抑制miRNA功能。然而，核酸的大尺寸、亲水性、负电荷和核酸酶敏感性需要合适的载体将其作为药物引入细胞。
虽然为此目的已经研究了许多有机和无机材料，但完美的载体仍然难以捉摸。由于其可调谐的表面特性以及机械、电学、光学和化学性质，碳基纳米材料最近在生物技术中受到了广泛关注。
