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Injectable redox and light responsive MnO2 hybrid hydrogel for simultaneous melanoma therapy and multidrug-resistant bacteria-infected wound healing.
Biomaterials ( IF 14.0 ) Pub Date : 2020-08-12 , DOI: 10.1016/j.biomaterials.2020.120314
Shenqiang Wang 1 , Hua Zheng 1 , Li Zhou 1 , Fang Cheng 1 , Zhao Liu 1 , Hepeng Zhang 1 , Qiuyu Zhang 2
Affiliation  

The recurrence of cutaneous cancer and multidrug-resistant (MDR) bacteria infected-wound healing after surgical excision remains a great challenge for both clinic and research. In this study, we developed an injectable redox and light responsive bio-inspired MnO2 hybrid (BMH) hydrogel for effective melanoma photothermo-chemotherapy and MDR bacteria infected-wound healing. The BMH hydrogel was ingeniously fabricated via non-covalent self-assembly and MnO2 nanosheets mediated covalent oxidative polymerization of the catechol functionalized chitosan for the first time. The BMH hydrogel displayed excellent shear-thinning, injectable, adhesive, redox/light responsive and contact-active antibacterial capabilities. Remarkably, our rationally designed BMH hydrogel could alleviate the hypoxic tumor microenvironment (TME) by decomposing the endogenous H2O2 into O2, and simultaneously release anticancer drug DOX. Increasing the local availability of O2 enhanced the cytotoxicity of DOX against melanoma in a highly site-specific manner. By further combining with a spatiotemporal controllable photothermal hyperthermia, we demonstrated a near-complete tumor suppression both in vitro (98.6%) and large solid tumors in vivo (96.2%). Moreover, BMH hydrogel could significantly promote the MDR-infected wound healing in vivo by efficiently eradicating bacterial invasion and perpetually ameliorating the oxidative and inflammatory wound microenvironment. Collectively, BMH hydrogel indicated great therapeutic potentials for both cancer therapy and tissue engineering.



中文翻译:

可注射的氧化还原和光响应性MnO2杂合水凝胶可用于同时进行黑色素瘤治疗和耐多药细菌感染的伤口愈合。

外科切除后皮肤癌和多药耐药菌感染伤口的愈合对于临床和研究仍然是一个巨大的挑战。在这项研究中,我们开发了一种可注射的氧化还原和光响应性生物启发性MnO 2杂化(BMH)水凝胶,用于有效的黑色素瘤光热化学疗法和MDR细菌感染的伤口愈合。BMH水凝胶是通过非共价自组装和MnO 2巧妙地制备的纳米片首次介导了邻苯二酚官能化壳聚糖的共价氧化聚合。BMH水凝胶具有出色的剪切稀化性,可注射性,粘合性,氧化还原/光响应性和接触活性抗菌能力。值得注意的是,我们合理设计的BMH水凝胶可通过将内源性H 2 O 2分解为O 2来缓解缺氧性肿瘤微环境(TME),同时释放抗癌药物DOX。O 2的局部可用性的增加以高度位点特异性的方式增强了DOX对黑色素瘤的细胞毒性。通过进一步结合时空可控的光热热疗,我们证明了在体外均具有近乎完全的肿瘤抑制作用(98.6%)和体内大型实体瘤(96.2%)。此外,BMH水凝胶可通过有效消除细菌入侵并永久改善氧化性和炎症性伤口微环境,从而显着促进体内感染MDR的伤口愈合。总体而言,BMH水凝胶在癌症治疗和组织工程设计中均显示出巨大的治疗潜力。

更新日期:2020-08-25
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