Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.
Single-walled carbon nanotubes noncovalently functionalized with lipid modified polyethylenimine for siRNA delivery in vitro and in vivo.
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DOI：
10.1021/bc500280q
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发表时间：
2014-09
影响因子：
4.7
通讯作者：
K. Siu;Xiufen Zheng;Yanling Liu;Yujuan Zhang;Xusheng Zhang;Di Chen;Ken Yuan;E. Gillies;J. Kor
中科院分区：
文献类型：
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作者：
K. Siu;Xiufen Zheng;Yanling Liu;Yujuan Zhang;Xusheng Zhang;Di Chen;Ken Yuan;E. Gillies;J. Kor
siRNA可以下调特定基因的表达。然而，将其递送至体内特定细胞和组织面临着巨大的挑战。修饰碳纳米管 (CNT) 已被证明可以保护 siRNA 并促进其进入细胞。然而，需要简单有效的方法来功能化碳纳米管。在此，对 CNT 进行非共价功能化，并显示可以有效地将 siRNA 递送至靶细胞。具体来说，单壁碳纳米管通过与脂聚合物非共价结合而被功能化。脂质聚合物（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比例的聚乙烯亚胺（PEI）与 DSPE-PEG，并将产物用于分散碳纳米管。所得材料用于体外和体内 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。该材料的细胞毒性较低，并且在体外证明了 B16-F10 细胞中有效的基因沉默。此外，静脉注射后发现肝脏中 siRNA 的显着吸收以及基因沉默。这种方法为 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 CNT 提供见解。
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.