Injectable, NIR/pH-Responsive Nanocomposite Hydrogel as Long-Acting Implant for Chemophotothermal Synergistic Cancer Therapy
Injectable, NIR/pH-Responsive Nanocomposite Hydrogel as Long-Acting Implant for Chemophotothermal Synergistic Cancer Therapy
复制标题
可注射、NIR/pH 响应的纳米复合水凝胶作为化学光热协同癌症治疗的长效植入物
DOI：
10.1021/acsami.7b02307
复制
发表时间：
2017-06-21
影响因子：
9.5
通讯作者：
Zhao, Chunshun
中科院分区：
文献类型：
--
作者：
Xu, Xiaoyu;Huang, Ziyuan;Zhao, Chunshun
在本研究中，将金纳米棒（GNRs）加入到n -异丙基丙烯酰胺（NIPAm）和甲基丙烯酸化聚β -葡糊精（MPCD）大分子共聚形成的水凝胶网络中，制备了一种可注射的近红外(NIR)/ ph响应的聚(NIPAm- MPCD)/GNRs纳米复合水凝胶，该水凝胶可作为长效植入物用于化学光热协同癌症治疗。纳米复合水凝胶具有优异的力学性能、溶胀性能、凝胶特性和优异的nir响应性能。疏水酸不稳定的金刚烷修饰阿霉素（AD-DOX）前药通过主客体相互作用被高效地装载到水凝胶中。纳米复合水凝胶具有缓释作用，可使DOX缓释1个月以上。在酸性环境下，由于DOX与金刚烷基之间的酸不稳定的腙键断裂，使得纳米复合水凝胶中DOX的ph响应性释放。近红外辐射可以加速DOX从网络中的释放，这是由gnr光热效应引起的水凝胶网络崩溃控制的。体外细胞毒性实验表明，纳米复合水凝胶具有良好的生物相容性和光热效应。此外，原位形成的水凝胶在小鼠模型研究中显示出良好的组织生物相容性。体内抗肿瘤试验表明，纳米复合水凝胶具有光热化学协同治疗的能力，由于药物在肿瘤区域的滞留时间延长和光热效应有效，副作用减少。因此，这种可注射且具有近红外/ ph响应的纳米复合水凝胶作为化学光热协同癌症治疗的长期药物传递平台具有很大的潜力。
In this study, gold nanorods (GNRs) were incorporated into the hydrogel networks formed by the copolymerization of N-isopropylacrylamide (NIPAm) and methacrylated poly-beta-cydodextrin (MPCD)-based macromer to fabricate an injectable and near-infrared (NIR)/pH-responsive poly(NIPAm-co-MPCD)/GNRs nanocomposite hydrogel, which could serve as a long-acting implant for chemophotothermal synergistic cancer therapy. The nano composite hydrogel showed superior mechanical and swelling properties, gelation characteristics, and excellent NIR-responsive property. A hydrophobic acid-labile adamantane-modified doxorubicin (AD-DOX) prodrug was loaded into the hydrogel efficiently by host guest interaction. The nanocomposite hydrogel exhibited a manner of sustained drug release and could sustain the slow and steady release of DOX for more than 1 month. The pH-responsive release of DOX from the nanocomposite hydrogel was observed owing to the cleavage of acid-labile hydrazone bond between DOX and the adamantyl group in acidic environment. NIR irradiation could accelerate the release of DOX from the networks, which was controlled by the collapse of the hydrogel networks induced by photothermal effect of GNRs. The in vitro cytotoxicity test demonstrated the excellent biocompatibility and photothermal effect of the nanocomposite hydrogel. Moreover, the in situ-forming hydrogel showed promising tissue biocompatibility in the mouse model study. The in vivo antitumor test demonstrated the capacity of the nanocomposite hydrogel for chemophotothermal synergistic therapy with reduced adverse effects owing to the prolonged drug retention in the tumor region and efficient photothermal effect. Therefore, this injectable and NIR/pH-responsive nanocomposite hydrogel exhibited great potential as a long term drug delivery platform for chemophotothermal synergistic cancer therapy.