Enhance chemotherapy efficacy and minimize anticancer drug side effects by using reversibly pH- and redox-responsive cross-linked unimolecular micelles
Enhance chemotherapy efficacy and minimize anticancer drug side effects by using reversibly pH- and redox-responsive cross-linked unimolecular micelles
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DOI：
10.1016/j.polymer.2017.03.062
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发表时间：
2017-05-05
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;Abuali, Maryam;Niknejad, Hassan
在保持原有治疗优势的同时消除化疗副作用是近几十年来引起广泛关注的问题。我们在此开发了一种新的pH和氧化还原敏感的纳米凝胶谷胱甘肽介导的细胞内药物输送采用二硫键交联单分子胶束。我们开发了H40-聚己内酯-b-聚丙烯酸-b '-甲氧基聚（乙二醇）/聚（乙二醇）-叶酸酯（即，H40-PCL-（b-PAA-b '-MPEG/PEG-FA）（2））单分子胶束，其在外围具有靶向部分。然后将其与胱胺交联以产生pH和氧化还原敏感的纳米凝胶。进行动态光散射（DLS）以研究pH依赖性纳米凝胶尺寸。我们将紫杉醇，一种疏水性的抗癌药物，应用到传递系统中，并研究了在不同pH值下DTT缓冲液暴露时的触发释放行为。我们的研究结果表明，DTT作为还原剂在酸性环境中的存在是必不可少的药物释放。这可以潜在地减少非癌性酸性组织处的不需要的药物释放，从而消除副作用。我们使用MTT法检测了游离纳米凝胶和载PTX纳米凝胶对正常和癌HeLa细胞的生物相容性和细胞毒性。通过将黄绿素加载到凝胶中，然后通过荧光显微镜成像来确认纳米凝胶HeLa细胞摄取。我们的新策略将在增强化疗疗效和最小化副作用方面产生深远的影响。(C)2017爱思唯尔有限公司版权所有
Chemotherapy side effects elimination while keeping the original therapeutic advantages has been of extensive interest over last decades. We herein develope a new pH and redox-sensitive nanogel for glutathione-mediated intracellular drug delivery employing disulfide crosselinked unimolecular micelles. We developed H40-polycaprolactone-b-polyacrylic acid-b'-methoxy poly(ethylene glycol)/poly(-ethylene glycol)-folate (i.e., H40-PCL-(b-PAA-b'-MPEG/PEG-FA)(2)) unimolecular micelles with targeting moieties on the periphery. It was then crosslinked with cystamine in order to generate a pH and redox-sensitive nanogel. Dynamic light scattering (DLS) was performed to study pH-dependent nanogel sizes. We applied Paclitaxel, a hydrophobic anticancer drug, into delivery system and examined triggered release behaviors at different pHs upon DTT buffer exposure. Our results demonstrated that DTT presence as reductive agent within acidic environment is essential for drug release. This may potentially reduce unwanted drug release at non-cancerous acidic tissues leading to eliminated side effects. We examined biocompatibility and cytotoxicity of free nanogel and PTX-loaded nanogel to normal and cancer HeLa cells using MTT assay. Nanogel HeLa cell uptake was confirmed by Fluorescein loading into the gel followed by fluorescent microscope imaging. Our novel strategy would have profound implications in both enhanced chemotherapy efficacy and minimized side effects. (C) 2017 Elsevier Ltd. All rights reserved.