Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy
Hollow mesoporous silica nanoparticles facilitated drug delivery via cascade pH stimuli in tumor microenvironment for tumor therapy
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DOI：
10.1016/j.biomaterials.2016.01.008
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发表时间：
2016-03-01
期刊：
影响因子：
14
通讯作者：
Cai, Kaiyong
中科院分区：
文献类型：
--
作者：
Liu, Junjie;Luo, Zhong;Cai, Kaiyong
为了有效地将抗癌药物递送到肿瘤部位并降低其对正常组织的毒副作用，制备了聚乙二醇（PEG）屏蔽和肿瘤微环境触发级联pH响应中空介孔二氧化硅纳米粒子（HMSNs）药物递送系统。将3-（3，4-二羟基苯基）丙酸（DHPA）功能化的β-环糊精（β-CD）通过硼酸-邻苯二酚酯键接枝到HMSN 5表面。然后，通过宿主-阵风相互作用将PEG缀合的金刚烷（Ada）锚定在HMSN-β-CD纳米载体上。各种技术证明了该系统的成功制造。体外试验证实该系统具有生物相容性。HMSNs通过增强渗透和滞留（EPR）效应进入肿瘤后，在肿瘤微环境（pH6.8）中，PEG与Ada之间的苯甲酰亚胺键在弱酸条件下发生断裂，而解离的PEG保护层有利于HMSNs系统的细胞摄取。随后，硼酸-儿茶酚酯键接头在甚至低的内体pH（4.5-6.5）条件下进一步水解以用于细胞内药物递送，导致有效的细胞凋亡。体内结果表明，载药HMSNs显着抑制肿瘤生长，而只有最小的毒副作用。该策略为开发由肿瘤微环境触发的新一代药物递送载体提供了新的见解。(C)2016爱思唯尔有限公司版权所有
To efficiently deliver anti-cancer drug to tumor site and reduce its toxic side effects on normal tissues, a polyethylene glycol (PEG) shielding and tumor microenvironment triggering cascade pH-responsive hollow mesoporous silica nanoparticles (HMSNs) drug delivery system was fabricated. 3-(3, 4-dihydroxyphenyl) propionic acid (DHPA) functionalized beta-cyclodextrin (beta-CD) was grafted onto the surfaces of HMSN5 via boronic acid-catechol ester bonds. Then, PEG conjugated adamantane (Ada) was anchored on HMSNs-beta-CD nanocarrier via host-gust interaction. Various techniques proved the successful fabrication of the system. The in vitro tests confirmed that the system was biocompatible. After the system permeating into tumor via enhanced permeability and retention (EPR) effect, the benzoicimine bonds between the PEG and Ada were cleaved under weak acid condition in tumor microenvironment (pH 6.8), while the dissociated PEG protective layer facilitating cellular uptake of HMSNs system. Subsequently, the boronic acid-catechol ester bonds linkers further hydrolyzed under even low endosomal pH (4.5-6.5) condition for intracellular drug delivery, leading to efficient cell apoptosis. The in vivo results demonstrated that drug loaded HMSNs significantly inhibited tumor growth while only with minimal toxic side effects. The strategy provides new insight into the development of new generation of drug delivery carriers triggering by tumor microenvironment. (C) 2016 Elsevier Ltd. All rights reserved.