Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity
Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity
复制标题
具有肿瘤特异性的功能化中空介孔二氧化硅纳米储库的细胞内氧化还原激活抗癌药物递送
DOI：
10.1016/j.biomaterials.2014.05.058
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发表时间：
2014-09-01
期刊：
影响因子：
14
通讯作者：
Zhao, Yanli
中科院分区：
文献类型：
--
作者：
Luo, Zhong;Hu, Yan;Zhao, Yanli
在这项研究中，开发了一种具有肿瘤特异性的细胞内氧化还原触发的中空介孔二氧化硅纳米储库（HMSN），以递送抗癌药物（即，多柔比星（DOX））对靶肿瘤细胞具有高治疗效率和降低的副作用。首先，使用可氧化还原裂解的二硫键作为中间连接体将金刚烷胺接枝到HMSN的孔上。随后，合成的功能分子，乳糖酸-接枝-β-环糊精（β-CD-LA），通过与金刚烷基的特异性络合固定在HMSN的表面上，其中β-CD作为封端剂，以保持负载的药物在HMSN内。HMSN上的β-CD-LA也可以作为针对肿瘤细胞的靶向剂（即，HepG2细胞），因为β-CD-LA中的乳糖基团是与HepG2细胞上的脱唾液酸糖蛋白受体（ASGP-R）结合的特异性配体。体外研究表明，DOX纳米储库可以被HepG2细胞选择性内吞，将治疗性DOX释放到细胞质中，并有效地诱导细胞凋亡和细胞死亡。体内研究进一步证实，载药纳米库可以渗透到肿瘤部位，并与肿瘤细胞积极相互作用，抑制肿瘤生长，副作用最小化。总体而言，该药物传递系统作为一种有效的载体，在体外和体内肿瘤靶向治疗中显示出巨大的潜力。(C)2014爱思唯尔有限公司版权所有。
In this study, a type of intracellular redox-triggered hollow mesoporous silica nanoreservoirs (HMSNs) with tumor specificity was developed in order to deliver anticancer drug (i.e., doxorubicin (DOX)) to the target tumor cells with high therapeutic efficiency and reduced side effects. Firstly, adamantanamine was grafted onto the orifices of HMSNs using a redox-cleavable disulfide bond as an intermediate linker. Subsequently, a synthetic functional molecule, lactobionic acid-grafted-beta-cyclodextrin (beta-CD-LA), was immobilized on the surface of HMSNs through specific complexation with the adamantyl group, where beta-CD served as an end-capper to keep the loaded drug within HMSNs. beta-CD-LA on HMSNs could also act as a targeting agent towards tumor cells (i.e., HepG2 cells), since the lactose group in beta-CD-LA is a specific ligand binding with the asialoglycoprotein receptor (ASGP-R) on HepG2 cells. In vitro studies demonstrated that DOX-loaded nanoreservoirs could be selectively endocytosed by HepG2 cells, releasing therapeutic DOX into cytoplasm and efficiently inducing the apoptosis and cell death. In vivo investigations further confirmed that DOX-loaded nanoreservoirs could permeate into the tumor sites and actively interact with tumor cells, which inhibited the tumor growth with the minimized side effect. On the whole, this drug delivery system exhibits a great potential as an efficient carrier for targeted tumor therapy in vitro and in vivo. (C) 2014 Elsevier Ltd. All rights reserved.