School of Pharmaceutical Sciences, Sun Yat-sen University , 132 Waihuan East Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, P. R. China.
ACS Appl Mater Interfaces. 2017 Jun 21;9(24):20361-20375. doi: 10.1021/acsami.7b02307. Epub 2017 Jun 7.
In this study, gold nanorods (GNRs) were incorporated into the hydrogel networks formed by the copolymerization of N-isopropylacrylamide (NIPAm) and methacrylated poly-β-cyclodextrin (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 nanocomposite 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.
在这项研究中，金纳米棒（GNRs）被掺入到由 N-异丙基丙烯酰胺（NIPAm）和甲基丙烯酰化聚-β-环糊精（MPCD）基大分子单体共聚形成的水凝胶网络中，以制备可注射的近红外（NIR）/pH 响应的聚（NIPAm-co-MPCD）/GNRs 纳米复合水凝胶，该水凝胶可作为化学光热协同癌症治疗的长效植入物。纳米复合水凝胶表现出优异的机械和溶胀性能、凝胶特性和出色的近红外响应性能。通过主客体相互作用，将疏水性酸不稳定的金刚烷改性阿霉素（AD-DOX）前药有效负载到水凝胶中。纳米复合水凝胶表现出持续的药物释放方式，可以持续缓慢稳定地释放 DOX 超过 1 个月。由于在酸性环境中 DOX 与金刚烷基之间的酸不稳定腙键的断裂，观察到纳米复合水凝胶中 DOX 的 pH 响应释放。NIR 照射可以加速 DOX 从网络中的释放，这是由 GNRs 的光热效应引起的水凝胶网络塌陷控制的。体外细胞毒性试验表明了纳米复合水凝胶具有优异的生物相容性和光热效应。此外，在小鼠模型研究中，原位形成的水凝胶表现出良好的组织生物相容性。体内抗肿瘤试验表明，由于在肿瘤区域中药物保留时间延长和有效的光热效应，纳米复合水凝胶具有用于化学光热协同治疗的能力，从而减少了不良反应。因此，这种可注射的 NIR/pH 响应纳米复合水凝胶作为用于化学光热协同癌症治疗的长效药物递送平台具有很大的潜力。
