NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor.
NIR-triggered thermo-responsive biodegradable hydrogel with combination of photothermal and thermodynamic therapy for hypoxic tumor.
复制标题
近红外触发热响应生物可降解水凝胶结合光热和热力学疗法治疗缺氧肿瘤
DOI：
10.1016/j.ajps.2019.11.007
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发表时间：
2020-11
影响因子：
10.2
通讯作者：
Zhao C
中科院分区：
文献类型：
--
作者：
Sun X;Liu D;Xu X;Shen Y;Huang Y;Zeng Z;Xia M;Zhao C
低氧是实体瘤的典型特征，极大地限制了氧依赖治疗的应用。此外，致密和高压的肿瘤组织阻碍了纳米颗粒对深层肿瘤的渗透。因此，我们设计了一种新型的局部注射水凝胶，它结合了光热疗法(PTT)和热力学疗法(TDT)，它是基于即使在缺氧的情况下也能产生自由基来治疗肿瘤的。在我们的研究中，金纳米棒(AuNRs)和2，2‘-偶氮二[2-(2-咪唑啉-2-基)丙烷]二氢氯代(AIPH)被引入到由疏水的N-异丙基丙烯酰胺(NIPAM)和亲水的甲基丙烯酸缩水甘油酯改性的透明质酸(HA-GMA)共聚形成的水凝胶网络中，制备了一种可注射的近红外(NIR)响应型水凝胶。原位形成的交联水凝胶不仅能在近红外激光照射下实现PTT，而且即使在低氧条件下也能产生自由基。同时，水凝胶受热收缩会加速自由基的产生，进一步损伤肿瘤，实现药物按需可控释放。所设计的水凝胶具有足够的负载量、良好的生物相容性和可忽略的全身毒性，可以作为一种长效植入剂用于近红外引发的温度响应性自由基的产生。体外细胞毒性和体内抗肿瘤活性表明，即使在无氧条件下，水凝胶仍具有良好的治疗效果。因此，这种结合了PTT和TDT抗肿瘤作用的创新型氧非依赖平台将为应用烷基自由基进行低氧肿瘤治疗带来新的视角。由HA-GMA和NIPAM组成的水凝胶的形成示意图，负载AIPH和AuNRs以及光热和热力学治疗的组合用于低氧肿瘤的治疗。
Hypoxia is a typical feature of solid tumors, which highly limits the application of the oxygen-dependent therapy. Also, the dense and hyperbaric tumor tissues impede the penetration of nanoparticles into the deep tumor. Thereby, we designed a novel localized injectable hydrogel combining the photothermal therapy (PTT) and the thermodynamic therapy (TDT), which is based on the generation of free radicals even in the absence of oxygen for hypoxic tumor therapy. In our study, gold nanorods (AuNRs) and 2,2′-Azobis[2-(2-imidazalin-2-yl)propane] dihydrochlaride (AIPH) were incorporated into the hydrogel networks, which were formed by the copolymerization of hydrophobic N-isopropyl acrylamide (NIPAM) and hydrophilic glycidyl methacrylate modified hyaluronic acid (HA-GMA) to fabricate an injectable and near-infrared (NIR) responsive hydrogel. The crosslinked in situ forming hydrogel could not only realize PTT upon the NIR laser irradiation, but also generate free radicals even in hypoxic condition. Meanwhile the shrink of hydrogels upon thermal could accelerate the generation of free radicals to further damage the tumors, achieving the controlled drug release on demand. The designed hydrogel with a sufficient loading capacity, excellent biocompatibility and negligible systemic toxicity could serve as a long-acting implant for NIR-triggered thermo-responsive free radical generation. The in vitro cytotoxicity result and the in vivo antitumor activity illustrated the excellent therapeutic effect of hydrogels even in the absence of oxygen. Therefore, this innovative oxygen-independent platform combining the antitumor effects of PTT and TDT would bring a new insight into hypoxic tumor therapy by the application of alkyl free radical. Schematic illustration of the formation of the hydrogels composed of HA-GMA and NIPAM, loaded with AIPH and AuNRs and the combination of the photothermal and thermodynamic therapy for hypoxic tumor therapy.
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影响因子：
14
作者：
Patterson J;Siew R;Herring SW;Lin AS;Guldberg R;Stayton PS
通讯作者：
Stayton PS
影响因子：
6.1
作者：
Liao, Wenzhen;Ning, Zhengxiang;Ren, Jiaoyan
通讯作者：
Ren, Jiaoyan
影响因子：
--
作者：
Offor, Ugochukwu;Naidu, Edwin Coleridge;Azu, Onyemaechi Okpara
通讯作者：
Azu, Onyemaechi Okpara
影响因子：
9.5
作者：
Shi, Kun;Liu, Zhuang;Chu, Liang-Yin
通讯作者：
Chu, Liang-Yin
影响因子：
29.4
作者：
Annabi, Nasim;Tamayol, Ali;Uquillas, Jorge Alfredo;Akbari, Mohsen;Bertassoni, Luiz E.;Cha, Chaenyung;Camci-Unal, Gulden;Dokmeci, Mehmet R.;Peppas, Nicholas A.;Khademhosseini, Ali
通讯作者：
Khademhosseini, Ali