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1.
Bioconjug Chem ; 25(10): 1744-51, 2014 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-25216445

RESUMO

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.


Assuntos
Nanotubos de Carbono/química , Polietilenoimina/química , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular , Humanos , Fígado/metabolismo , Camundongos , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Interferência de RNA , RNA Interferente Pequeno/genética , Transfecção
2.
Biomaterials ; 35(10): 3435-42, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24424208

RESUMO

RNAi can specifically regulate gene expression, but efficient delivery of siRNA in vivo is difficult while it has been shown that modified carbon nanotubes (CNT) protect siRNA, facilitate entry into cells and enhance transdermal drugs delivery. Single-walled carbon nanotubes (SWCNT) were functionalized non-covalently with succinated polyethyleimine (PEI-SA). In this study, the water soluble CNT, PEI-SA/CNT (IS/C) were isolated and characterized, the gene silencing induced by IS/C/siRNA complexes was achieved in vitro in B16-F10 cells. In vivo delivery was topically applied to shaved mouse skin, as well as topically to a C57BL/6 mice melanoma model. We found significant uptake of Cy3-labeled siRNA specific to Braf (siBraf) and gene silencing in the tumor tissue. Treatment with IS/C/siBraf resulted in attenuation of tumor growth over a 25-day period. This new delivery method has provided a new possibility for future siRNA delivery and therapy, which providing insight for the potential application and development of CNT-based siRNA delivery.


Assuntos
Melanoma Experimental/tratamento farmacológico , Nanotubos de Carbono , RNA Interferente Pequeno/administração & dosagem , Animais , Inativação Gênica , Melanoma Experimental/genética , Camundongos , Camundongos Endogâmicos C57BL , RNA Interferente Pequeno/uso terapêutico
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