A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.
A Novel Stimuli-Responsive Injectable Antibacterial Hydrogel to Achieve Synergetic Photothermal/Gene-Targeted Therapy towards Uveal Melanoma.
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一种新型刺激响应型可注射抗菌水凝胶，可实现葡萄膜黑色素瘤的光热/基因靶向协同治疗
DOI：
10.1002/advs.202004721
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发表时间：
2021-09
期刊：
影响因子：
--
通讯作者：
Jia R
中科院分区：
文献类型：
--
作者：
Wang S;Chen B;Ouyang L;Wang D;Tan J;Qiao Y;Ge S;Ruan J;Zhuang A;Liu X;Jia R
葡萄膜黑色素瘤（Uvealmelanoma，UM）是最常见的原发性眼内恶性肿瘤，致死率高.接受常规眼球摘除术治疗的患者持续遭受永久性失明、面部缺陷和精神障碍，因此，迫切需要新的治疗方式。本文中，通过受传统中药制备工艺启发的简易研磨方法构建可注射和刺激响应性药物递送抗菌水凝胶（CP @ Au @ DC_AC 50）。金纳米棒的掺入可以增强水凝胶的机械强度，并实现光热治疗（PTT）和热敏凝胶-溶胶转化，以响应低密度近红外（NIR）光按需释放基因靶向药物DC_AC50。成功建立了UM的原位模型，并表明CP @ Au @ DC_AC 50在杀死肿瘤而不损伤正常组织方面具有优异的效率，这是因为其协同的温和温度PTT和基因靶向治疗。此外，眼球感染模型揭示了水凝胶的显著抗菌特性，其可以预防眼球中的眼内炎。CP@Au@DC_AC50+NIR组与正常组之间的差异可忽略不计。这种NIR光触发基因靶向治疗/PTT/抗菌治疗模式为构建眼内肿瘤的多功能治疗平台提供了一种有前景的策略，并在UM的临床治疗中显示出巨大的潜力。受传统中药制备中研磨方法的启发，首次构建了可注射抗菌自组装水凝胶-- CP@Au@DC_AC50的NIR光触发药物释放/光热/基因靶向治疗在体外和体内均表现出出色的协同抗肿瘤和抗菌功效，而不会损伤眼内组织。基因靶向治疗/PTT/抗菌平台具有未来应用于眼部肿瘤治疗的潜力。
Uveal melanoma (UM) is the most prevalent primary intraocular malignant tumor with a high lethal rate. Patients who undergo conventional enucleation treatments consistently suffer permanent blindness, facial defects, and mental disorders, therefore, novel therapeutic modalities are urgently required. Herein, an injectable and stimuli‐responsive drug delivery antibacterial hydrogel (CP@Au@DC_AC50) is constructed via a facile grinding method that is inspired by the preparation process of traditional Chinese medicine. The incorporation of gold nanorods can enhance the mechanical strength of the hydrogel and realize photothermal therapy (PTT) and thermosensitive gel‐sol transformation to release the gene‐targeted drug DC_AC50 on demand in response to low‐density near‐infrared (NIR) light. The orthotopic model of UM is built successfully and indicates the excellent efficiency of CP@Au@DC_AC50 in killing tumors without damage to normal tissue because of its synergistic mild temperature PTT and gene‐targeted therapy. Moreover, the eyeball infection model reveals the remarkable antibacterial properties of the hydrogel which can prevent endophthalmitis in the eyeball. There is negligible difference between the CP@Au@DC_AC50+NIR group and normal group. This NIR light‐triggered gene‐targeted therapy/PTT/antibacterial treatment pattern provides a promising strategy for building multifunctional therapeutic platform against intraocular tumors and exhibits great potential for the clinical treatment of UM. Inspired by the grinding method in traditional Chinese medicine preparation, the injectable antibacterial self‐assembling nanofiber CP@Au@DC_AC50 hydrogels are first constructed. NIR light‐triggered drug release/photothermal/gene‐targeted therapy of CP@Au@DC_AC50 exhibits brilliant synergistic antitumor and antibacterial efficiency without damage to intraocular tissue in vitro and in vivo. The gene‐targeted therapy/PTT/antibacterial platform has potential for future application in ocular tumor therapy.
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