State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Immunology and Oncology Center, ICE Bioscience, Beijing, 100176, China.
Adv Sci (Weinh). 2024 Jul;11(26):e2402208. doi: 10.1002/advs.202402208. Epub 2024 May 5.
Surgical resection remains the mainstream treatment for malignant melanoma. However, challenges in wound healing and residual tumor metastasis pose significant hurdles, resulting in high recurrence rates in patients. Herein, a bioactive injectable hydrogel (BG-Mn) formed by crosslinking sodium alginate (SA) with manganese-doped bioactive glass (BG-Mn) is developed as a versatile platform for anti-tumor immunotherapy and postoperative wound healing for melanoma. The incorporation of Mn within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn in BG endows system with excellent photothermal properties, hence facilitating STING activation and reversing the tumor immune-suppressive microenvironment. BG exhibits favorable angiogenic capacity and tissue regenerative potential, and Mn promotes cell migration in vitro. When combining BG-Mn with anti-PD-1 antibody (α-PD-1) for the treatment of malignant melanoma, it shows enhanced anti-tumor immune response and long-term immune memory response. Remarkably, BG-Mn can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-Mn serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.
手术切除仍然是恶性黑色素瘤的主流治疗方法。然而,伤口愈合和残留肿瘤转移的挑战构成了重大障碍,导致患者的复发率很高。在此,开发了一种由海藻酸钠(SA)与掺锰生物活性玻璃(BG-Mn)交联形成的生物活性可注射水凝胶(BG-Mn),作为用于黑色素瘤的抗肿瘤免疫疗法和术后伤口愈合的多功能平台。在生物活性玻璃(BG)中掺入 Mn 可以激活 cGAS-STING 免疫途径,引发针对癌症免疫疗法的强大免疫反应。此外,BG 中 Mn 的掺杂赋予系统优异的光热性能,从而促进 STING 的激活和逆转肿瘤免疫抑制微环境。BG 表现出良好的血管生成能力和组织再生潜力,并且 Mn 促进细胞在体外迁移。当将 BG-Mn 与抗 PD-1 抗体(α-PD-1)联合用于治疗恶性黑色素瘤时,它显示出增强的抗肿瘤免疫反应和长期免疫记忆反应。值得注意的是,BG-Mn 可上调与血管形成相关的基因的表达并促进全层伤口的皮肤组织再生。总的来说,BG-Mn 可作为一种有效的辅助疗法,用于调节肿瘤转移和恶性黑色素瘤的伤口愈合。