Toub N, Malvy C, Fattal E, Couvreur P
Laboratoire de Physicochimie, Pharmacotechnie et Biopharmacie, UMR CNRS 8612, Faculté de Pharmacie, 5, rue Jean-Baptiste-Clement, 92286 Châtenay-Malabry cedex, France.
Biomed Pharmacother. 2006 Nov;60(9):607-20. doi: 10.1016/j.biopha.2006.07.093. Epub 2006 Aug 31.
One way to reach intracellular therapeutic targets in cells consists in the use of short nucleic acids which will bind specifically to on targets thanks to either Watson-Crick base pairing or protein nucleic acids recognition rules. Among these short nucleic acids an important class of therapeutic agents is antisense oligonucleotides and siRNAs. However, the major problem of nucleic acids is their poor stability in biological media. One method, among others, to solve the stability problem is the use of colloïdal carriers such as nanoparticles. Nanoparticles have already been applied with success to in vitro drug delivery to particular types of cells and in vivo in several experimental models. Many membrane and intracellular processes deal with nanosized structure (typically 100 nm) which are processed further through the recognition sites of receptors and enzymes. Thus non-viral nanoparticles are interesting candidates to present biochemical molecules such as nucleic acids and proteins to cells as well as to protect them in vivo during delivery. This review focuses on the recent developments in the design of nanotechnologies to improve the delivery of antisense oligonucleotides and siRNAs.
一种作用于细胞内治疗靶点的方法是使用短核酸,这些短核酸可通过沃森-克里克碱基配对或蛋白质核酸识别规则特异性结合靶点。在这些短核酸中,一类重要的治疗剂是反义寡核苷酸和小干扰RNA(siRNA)。然而,核酸的主要问题是它们在生物介质中的稳定性较差。解决稳定性问题的一种方法(还有其他方法)是使用胶体载体,如纳米颗粒。纳米颗粒已成功应用于体外向特定类型细胞的药物递送以及多种实验模型的体内递送。许多膜和细胞内过程涉及纳米尺寸的结构(通常为100纳米),这些结构会通过受体和酶的识别位点进一步处理。因此,非病毒纳米颗粒是将核酸和蛋白质等生化分子递送至细胞并在体内递送过程中保护它们的理想候选物。本综述重点关注纳米技术设计方面的最新进展,以改善反义寡核苷酸和小干扰RNA的递送。