pH/redox dual-sensitive dextran nanogels for enhanced intracellular drug delivery
pH/redox dual-sensitive dextran nanogels for enhanced intracellular drug delivery
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DOI：
10.1016/j.ejpb.2017.05.002
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发表时间：
2017-08-01
影响因子：
4.9
通讯作者：
Alvarez-Lorenzo, Carmen
中科院分区：
文献类型：
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作者：
Curcio, Manuela;Diaz-Gomez, Luis;Alvarez-Lorenzo, Carmen
以甲基丙烯酸葡聚糖（DEXMA）、甲基丙烯酸2-氨基乙酯（AEMA）和N，N '-双丙烯酰胱胺（BAC）为原料，通过沉淀聚合法制备pH/氧化还原双重响应纳米凝胶（DEX-SS），并负载甲氨蝶呤（MTX）。纳米凝胶是球形的，并且如使用动态光散射（DLS）和扫描电子显微镜（SEM）观察到的，显示出均匀的尺寸分布（460 nm，PDI < 0.30）。DEX-SS对pH和氧化还原环境的变化敏感。在含有10 mM谷胱甘肽（GSH）的pH 5.0缓冲液中孵育的纳米凝胶协同地将平均直径和PDI分别增加至750 nm和0.42。体外释放实验在pH 7.4和5.0下进行，有和没有GSH。MTX在pH 5.0培养基中与10 mM GSH的累积释放是在pH 7.4无GSH时记录的5倍。使用成纤维细胞和肿瘤细胞来测试空白DEX-SS和MTX@DEX-SS纳米凝胶对细胞活力的影响。通过共聚焦显微镜和流式细胞术证明了pH对纳米凝胶内化到HeLa细胞中的显著影响。(C)2017爱思唯尔B. V.保留所有权利。
pH/redox dual-responsive nanogels (DEX-SS) were prepared by precipitation polymerization of methacrylated dextran (DEXMA), 2-aminoethylmethacrylate (AEMA) and N,N'-bis(acryloyl)cystamine (BAC), and then loaded with methotrexate (MTX). Nanogels were spherical and exhibited homogeneous size distribution (460 nm, PDI < 0.30) as observed using dynamic light scattering (DLS) and scanning electron microscopy (SEM). DEX-SS were sensitive to the variations of pH and redox environment. Nanogels incubated in buffer pH 5.0 containing 10 mM glutathione (GSH) synergistically increased the mean diameter and the PDI to 750 nm and 0.42, respectively. In vitro release experiments were performed at pH 7.4 and 5.0 with and without GSH. The cumulative release of MTX in pH 5.0 medium with 10 mM GSH was 5 fold higher than that recorded at pH 7.4 without GSH. Fibroblasts and tumor cells were used to tests the effects of blank DEX-SS and MTX@DEX-SS nanogels on cell viability. Remarkable influence of pH on nano gels internalization into HeLa cells was evidenced by means of confocal microscopy and flow cytometry. (C) 2017 Elsevier B.V. All rights reserved.