pH-sensitive nanogels based on Boltorn® H40 and poly(vinylpyridine) using mini-emulsion polymerization for delivery of hydrophobic anticancer drugs
pH-sensitive nanogels based on Boltorn® H40 and poly(vinylpyridine) using mini-emulsion polymerization for delivery of hydrophobic anticancer drugs
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DOI：
10.1016/j.polymer.2014.06.037
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发表时间：
2014-08-05
期刊：
影响因子：
4.6
通讯作者：
Niknejad, Hassan
中科院分区：
文献类型：
--
作者：
Abandansari, Hamid Sadeghi;Nabid, Mohammad Reza;Niknejad, Hassan
在本研究中，我们描述了一种新的结构的pH敏感的H40基纳米凝胶的点击反应，通过细乳液聚合的合成。以H40-聚己内酯（H40-PCL）树枝状大分子为核，聚乙烯基吡啶（PVP）为pH敏感交联剂，通过交联反应制备了纳米凝胶。聚乙二醇（PEG）侧基引入到PVP链的中间作为亲水链段，作为最终纳米凝胶的亲水壳层，以获得更好的分散性。将叶酸通过游离羧基结合到PEG的末端，用于靶向过表达叶酸受体的癌细胞，这些纳米凝胶具有pH敏感性，并且纳米凝胶的溶胀率与环境的pH密切相关。在这种细胞内递送方法中，纳米凝胶暴露于细胞溶胶的低pH环境中，引发纳米凝胶膨胀并释放药物。用动态光散射（DLS）研究了pH敏感性。透射电子显微镜（TEM）和DLS分析表明，合成的纳米凝胶是均匀的，平均流体动力学直径约150 nm。采用紫外可见分光光度法研究了载药纳米凝胶对紫杉醇（PTX）的载药能力，以及载药纳米凝胶在不同pH下的释药规律。叶酸缀合的纳米凝胶可以通过叶酸受体介导的内吞作用被癌细胞内化。通过将荧光染料黄绿素负载到纳米凝胶中并拍摄荧光显微镜照片来评估细胞摄取。在体外评价最终纳米凝胶的细胞毒性。结果表明，合成的纳米凝胶是一个合适的候选人作为疏水性抗癌药物的纳米载体。(C)2014爱思唯尔有限公司版权所有。
In this study, we describe the synthesis of a new structure of pH-sensitive H40 based nanogel by click reaction through mini-emulsion polymerization. The nanogels were synthesized by cross coupling of H40-poly(epsilon-caprolactone) (H40-PCL) dendrimers as cores and poly(vinylpyridine) (PVP) as a pH sensitive crosslinker. The poly(ethylene glycol) (PEG) pendant group was introduced at the middle of PVP chains as hydrophilic segment to act as hydrophilic shell at final nanogel for better dispersity. Folic acid that is conjugated at the end of some of PEG through the free carboxyl group was used for targeting cancer cells that overexpress folate receptors.These nanogels are pH-sensitive and swelling ratio of the nanogels is closely relevant to the pH of environment. In this intracellular delivery method, the nanogel was exposed to low-pH environments of cytosol that triggered the nanogel to swell and release the drug. pH-sensitive behavior were studied by means of dynamic light scattering (DLS). Transmission electron microscopy (TEM) and DLS analysis demonstrated that the synthesized nanogels are uniform with a mean hydrodynamic diameter around 150 nm. The loading capability of the nanogels for paclitaxel (PTX), and the release pattern of the drug-loaded nanogels at different pH were investigated by UV-vis spectrometry. The folate-conjugated nanogel can be internalized by the cancer cells via folate-receptor mediated endocytosis. Cell uptake was evaluated by loading of Fluorescein as fluorescent dye into the nanogel and take fluorescent microscope photo. Cytotoxicity of the final nanogel was evaluated in vitro. The results demonstrated that the synthesized nanogel is an appropriate candidate as a nanocarrier for hydrophobic anticancer drugs. (C) 2014 Elsevier Ltd. All rights reserved.