PDF(Pubmed)
Abstract：
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-Mngel) 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 Mn2+ within bioactive glass (BG) can activate the cGAS-STING immune pathway to elicit robust immune response for cancer immunotherapy. Furthermore, doping Mn2+ 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 Mn2+ promotes cell migration in vitro. When combining BG-Mngel 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-Mngel can upregulate the expression of genes related to blood vessel formation and promote skin tissue regeneration when treating full-thickness wounds. Overall, BG-MnGel serves as an effective adjuvant therapy to regulate tumor metastasis and wound healing for malignant melanoma.
摘要：
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，导致患者复发率高。在这里，通过海藻酸钠（SA）与锰掺杂的生物活性玻璃（BG-Mn）交联形成的生物活性可注射水凝胶（BG-Mngel）被开发为抗肿瘤免疫疗法和黑色素瘤术后伤口愈合的通用平台。在生物活性玻璃（BG）中掺入Mn2可以激活cGAS-STING免疫途径，以引发癌症免疫疗法的强大免疫反应。此外，在BG中掺杂Mn2使系统具有优异的光热性能，从而促进STING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，Mn2+促进体外细胞迁移。BG-Mngel与抗PD-1抗体（α-PD-1）联合治疗恶性黑色素瘤时，它显示出增强的抗肿瘤免疫应答和长期免疫记忆应答。值得注意的是,BG-Mngel在治疗全层伤口时可以上调与血管形成相关的基因的表达并促进皮肤组织再生。总的来说,BG-MnGel是一种有效的辅助疗法，可调节恶性黑色素瘤的肿瘤转移和伤口愈合。
