非共价功能化单壁碳纳米管用于黑素瘤的局部 siRNA 递药。
Non-covalently functionalized single-walled carbon nanotube for topical siRNA delivery into melanoma.
机构信息
Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada.
Department of Pathology, Western University, London, Canada; Department of Surgery, Western University, London, Canada; Department of Oncology, Western University, London, Canada; Department of Microbiology and Immunology, Western University, London, Canada; Department of Physiology and Pharmacology, Western University, London, Canada; Jiangxi Academy of Medical Sciences, and Institute of Immunomodulation and Immunotherapy of Nanchang University, Nanchang, China.
出版信息
Biomaterials. 2014 Mar;35(10):3435-42. doi: 10.1016/j.biomaterials.2013.12.079. Epub 2014 Jan 11.
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.
RNAi 可以特异性地调节基因表达，但体内有效的 siRNA 递呈很困难，而研究表明，经过修饰的碳纳米管（CNT）可以保护 siRNA，促进细胞摄取并增强经皮药物递送。本文用琥珀酸酐化聚亚乙基亚胺（PEI-SA）对单壁碳纳米管（SWCNT）进行非共价功能化。在这项研究中，分离并表征了水溶性 CNT、PEI-SA/CNT（IS/C），并在 B16-F10 细胞中实现了 IS/C/siRNA 复合物的体外基因沉默。体内递呈通过局部应用于剃毛小鼠皮肤以及 C57BL/6 小鼠黑素瘤模型进行。我们发现 Cy3 标记的针对 Braf（siBraf）的 siRNA 有明显的摄取，并在肿瘤组织中实现了基因沉默。用 IS/C/siBraf 治疗可导致肿瘤生长在 25 天内得到抑制。这种新的递呈方法为未来的 siRNA 递呈和治疗提供了新的可能性，为 CNT 基 siRNA 递呈的潜在应用和发展提供了思路。
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