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一种近红外二区光调控的可注射自修复水凝胶,用于协同光热/化学动力学/化学治疗黑色素瘤和促进伤口愈合。

A NIR-II light-modulated injectable self-healing hydrogel for synergistic photothermal/chemodynamic/chemo-therapy of melanoma and wound healing promotion.

机构信息

Guangxi Key Laboratory of Optical and Electronic Materials and Devices, and College of Materials Science and Engineering, Guilin University of Technology, Guilin 541004, P. R. China.

State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541001, China.

出版信息

J Mater Chem B. 2022 Oct 5;10(38):7717-7731. doi: 10.1039/d2tb00923d.


DOI:10.1039/d2tb00923d
PMID:35920389
Abstract

The development of an injectable multifunctional hydrogel with tumor therapy, antibacterial treatment and wound healing properties is essential for simultaneously eradicating melanoma and promoting wound healing of tumor-initiated skin defects. Herein, iron ion-doped polyaniline (PANI(Fe)) tethered with guar gum (GG) chains is employed for the first time as a building unit for constructing a superior hydrogel (GG@PANI(Fe)-borax) crosslinked by borate/didiol bonds. Due to the dynamic and reversible properties of boronate ester bonds, the GG@PANI(Fe)-borax hydrogels had convenient injectability, rapid self-healing ability, and reversible gel-sol transformations under thermal- or pH-stimuli. More importantly, they took advantage of the second near-infrared (NIR-II) responsive photothermal conversion capability, accompanied by the photothermal-enhanced high cytotoxic ˙OH generation in the HO-enriched tumor microenvironment induced by iron-doped PANI. The as-prepared hydrogels exhibited excellent photothermal effects and controllable NIR-triggered drug release, leading to distinctly synergistic photothermal/chemodynamic/chemo-therapy effects of melanoma both (98.2%) and (98.8%). In addition, the obtained hydrogels also exhibited good anti-bacterial activity (>97.1%) against both Gram-positive () and Gram-negative () bacteria because they were based on PANI(Fe) and borax, which exhibit antibacterial activity. Furthermore, these GG@PANI(Fe)-incorporated scaffolds could improve fibroblast cell proliferation and angiogenesis for accelerating wound repair in tumor-bearing and infected wound mice. Taken together, GG@PANI(Fe)-borax hydrogels may be used simultaneously for eradication of skin-tumor cells, inhibiting infection and accelerating wound healing. This work offers an effective and facile strategy to fabricate an "all-in-one" multifunctional hydrogel platform for synergetic multimodal integrated therapy of tumors.

摘要

开发具有肿瘤治疗、抗菌治疗和伤口愈合性能的可注射多功能水凝胶对于同时根除黑色素瘤和促进肿瘤引发的皮肤缺陷的伤口愈合至关重要。在此,首次将铁离子掺杂的聚苯胺(PANI(Fe))与瓜尔胶(GG)链键合,用作构建由硼酸盐/二二醇键交联的优越水凝胶(GG@PANI(Fe)-硼砂)的构建单元。由于硼酸酯键的动态和可逆性质,GG@PANI(Fe)-硼砂水凝胶具有方便的可注射性、快速的自修复能力以及在热或 pH 刺激下的凝胶-溶胶转变的可逆性。更重要的是,它们利用了第二个近红外(NIR-II)响应光热转换能力,伴随着铁掺杂 PANI 在富含 HO 的肿瘤微环境中诱导的光热增强的高细胞毒性˙OH 生成。所制备的水凝胶表现出优异的光热效应和可控制的 NIR 触发药物释放,导致黑色素瘤的光热/化学动力学/化疗协同作用明显(分别为 98.2%和 98.8%)。此外,由于基于具有抗菌活性的 PANI(Fe)和硼砂,所获得的水凝胶还表现出良好的抗菌活性(>97.1%),可抵抗革兰氏阳性()和革兰氏阴性()细菌。此外,这些含有 GG@PANI(Fe)的支架可以改善成纤维细胞的增殖和血管生成,从而加速荷瘤和感染伤口小鼠的伤口修复。总之,GG@PANI(Fe)-硼砂水凝胶可同时用于根除皮肤肿瘤细胞、抑制感染和加速伤口愈合。这项工作为同时根除皮肤肿瘤细胞、抑制感染和加速伤口愈合提供了一种有效且简便的策略,用于协同治疗肿瘤的多模式综合治疗。

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[3]
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[4]
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[6]
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[7]
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[9]
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