Siu King S, Zheng Xiufen, Liu Yanling, Zhang Yujuan, Zhang Xusheng, Chen Di, Yuan Ken, Gillies Elizabeth R, Koropatnick James, Min Wei-Ping
Departments of Pathology, Surgery, Oncology, Microbiology and Immunology, Physiology and Pharmacology and ∥Department of Chemistry, Chemical and Biochemical Engineering, University of Western Ontario , London, Ontario N6A 5H5, Canada.
Bioconjug Chem. 2014 Oct 15;25(10):1744-51. doi: 10.1021/bc500280q. Epub 2014 Sep 23.
siRNA can downregulate the expression of specific genes. However, delivery to specific cells and tissues in vivo presents significant challenges. Modified carbon nanotubes (CNTs) have been shown to protect siRNA and facilitate its entry into cells. However, simple and efficient methods to functionalize CNTs are needed. Here, noncovalent functionalization of CNTs is performed and shown to effectively deliver siRNA to target cells. Specifically, single-walled CNTs were functionalized by noncovalent association with a lipopolymer. The lipopolymer (DSPE-PEG) was composed of a phospholipid 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) and poly(ethylene glycol) (PEG). Three different ratios of polyethylenimine (PEI) to DSPE-PEG were synthesized and characterized and the products were used to disperse CNTs. The resulting materials were used for siRNA delivery in vitro and in vivo. The structural, biophysical, and biological properties of DGI/C and their complexes formed with siRNA were investigated. Cytotoxicity of the materials was low, and effective gene silencing in B16-F10 cells was demonstrated in vitro. In addition, significant uptake of siRNA as well as gene silencing in the liver was found following intravenous injection. This approach provides a new strategy for siRNA delivery and could provide insight for the development of noncovalently functionalized CNTs for siRNA therapy.
小干扰RNA（siRNA）能够下调特定基因的表达。然而，在体内将其递送至特定细胞和组织面临重大挑战。已证明修饰的碳纳米管（CNT）可保护siRNA并促进其进入细胞。然而，需要简单有效的方法来使CNT功能化。在此，进行了CNT的非共价功能化，并证明其能有效地将siRNA递送至靶细胞。具体而言，单壁碳纳米管通过与一种脂聚合物非共价结合而实现功能化。该脂聚合物（DSPE-PEG）由磷脂1,2-二硬脂酰-sn-甘油-3-磷酸乙醇胺（DSPE）和聚乙二醇（PEG）组成。合成并表征了三种不同聚乙烯亚胺（PEI）与DSPE-PEG的比例，所得产物用于分散碳纳米管。所得材料用于体外和体内的siRNA递送。研究了DGI/C及其与siRNA形成的复合物的结构、生物物理和生物学特性。材料的细胞毒性较低，并且在体外证明了其在B16-F10细胞中具有有效的基因沉默作用。此外，静脉注射后发现肝脏对siRNA有显著摄取以及基因沉默现象。该方法为siRNA递送提供了一种新策略，并可为开发用于siRNA治疗的非共价功能化碳纳米管提供思路。
