Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide.
Enhanced chemotherapy efficacy by sequential delivery of siRNA and anticancer drugs using PEI-grafted graphene oxide.
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DOI：
10.1002/smll.201001522
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发表时间：
2011-02
期刊：
影响因子：
13.3
通讯作者：
Liming Zhang;Zhuoxuan Lu;Qinghuan Zhao;Jie Huang;He Shen;Zhijun Zhang
中科院分区：
文献类型：
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作者：
Liming Zhang;Zhuoxuan Lu;Qinghuan Zhao;Jie Huang;He Shen;Zhijun Zhang
PEI GO RNA干扰（RNAi）技术是一种通过靶向切割信使RNA（mRNA）来抑制蛋白质表达的有效方法，自首次在哺乳动物细胞中证实基因敲减以来，已经取得了实质性进展。[ 1 ]短干扰RNA（Short interfering RNA，siRNA）可诱导靶蛋白的特异性沉默，从而为克服肿瘤细胞的多药耐药（multiple drug resistance，MDR）提供了重要的潜力。[ 2 ]例如，Bcl-2蛋白是主要的抗凋亡防御蛋白之一，与癌细胞的MDR密切相关。[ 3 ]通过Bcl-2靶向siRNA敲低癌细胞中Bcl-2蛋白的表达水平，将有效克服癌细胞的MDR，并使癌细胞对抗癌药物敏感。[3d，4 ]在本文中，我们报道了使用聚乙烯亚胺（PEI）官能化的氧化石墨烯（PEI-GO）顺序递送Bcl-2靶向siRNA和抗癌药物阿霉素（DOX）。我们证明了PEI-GO是一种用于有效递送siRNA和化学药物的优良纳米载体，并且通过PEI-GO将siRNA和DOX顺序递送到癌细胞中表现出协同效应，这导致显著增强的化疗效果。据我们所知，这是关于基于GO的纳米载体用于递送siRNA以及将siRNA和抗癌药物顺序递送到癌细胞中的应用的第一份报告。石墨烯是一种新发现的2D纳米材料，由于其重要性和潜在的应用而被广泛研究[ 5 ]，而其生物医学应用的探索才刚刚开始。[ 6 ]通过π - π堆积、静电和其他分子相互作用的非共价吸附已被证明可有效地将化学药物、单链DNA和RNA固定到GO片上。[ 6 a-e]
PEI GO The RNA interference (RNAi) technique, an effective method to inhibit protein expression by targeted cleavage of messenger RNA (mRNA), has made substantial progress since the fi rst demonstration of gene knockdown in mammalian cells. [ 1 ] Short interfering RNA (siRNA) induces specifi c silencing of targeted protein, thus offering signifi cant potential in overcoming multiple drug resistance (MDR) of cancer cells. [ 2 ] For example, Bcl-2 protein, one of the main antiapoptotic defense proteins, is closely related to the MDR of cancer cells. [ 3 ] Knockdown of the Bcl-2 protein expression level in cancer cells by Bcl-2-targeted siRNA would effectively overcome the MDR of cancer cells and sensitize cancer cells to anticancer drugs. [ 3 d, 4 ] Herein, we report sequential delivery of Bcl-2-targeted siRNA and the anticancer drug doxorubicin (DOX) using polyethylenimine (PEI)-functionalized graphene oxide (PEI-GO). We demonstrate that the PEI-GO is an excellent nanocarrier for effective delivery of siRNA and chemical drugs, and that sequential delivery of the siRNA and DOX by PEI-GO into cancer cells exhibits a synergistic effect, which leads to a signifi cantly enhanced chemotherapy effi cacy. To the best of our knowledge, this is the fi rst report on applications of GO-based nanovectors for delivery of siRNA, and sequential delivery of siRNA and anticancer drugs into cancer cells. Graphene, a newly discovered 2D nanomaterial, has been studied extensively due to its fundamental importance and potential applications, [ 5 ] while exploration of its biomedical applications has just started. [ 6 ] Noncovalent adsorption through π – π stacking, electrostatic, and other molecular interactions has proven to be effective for immobilizing chemical drugs, single-stranded DNA, and RNA onto GO sheets. [ 6 a–e]