Immunomodulatory hydrogel neutralizes tumor acidity to augment immune responses for the prevention of post-surgical recurrence of melanoma  

具有免疫调节作用的水凝胶中和肿瘤酸性以增强免疫用于防止黑色素瘤术后复发

作　　者：Zhiyuan Quan Linghui Chen Beibei Chen Kangli Guo Pengfei Tian Haobo Pan Yang Li Nana Zhao Fu-Jian Xu 全之嫄;陈凌卉;陈贝贝;郭康丽;田鹏飞;潘浩波;李杨;赵娜娜;徐福建(State Key Laboratory of Chemical Resource Engineering,Beijing University of Chemical Technology,Beijing 100029,China;Key Laboratory of Biomedical Materials of Natural Macromolecules(Beijing University of Chemical Technology),Beijing Laboratory of Biomedical Materials,Beijing University of Chemical Technology,Beijing 100029,China;College of Materials Sciences and Engineering,Beijing University of Chemical Technology,Beijing 100029,China;Center for Human Tissues and Organs Degeneration,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China)

机构地区：[1]State Key Laboratory of Chemical Resource Engineering,Beijing University of Chemical Technology,Beijing 100029,China [2]Key Laboratory of Biomedical Materials of Natural Macromolecules(Beijing University of Chemical Technology),Beijing Laboratory of Biomedical Materials,Beijing University of Chemical Technology,Beijing 100029,China [3]College of Materials Sciences and Engineering,Beijing University of Chemical Technology,Beijing 100029,China [4]Center for Human Tissues and Organs Degeneration,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

出　　处：《Science China Materials》2025年第1期270-279,共10页中国科学(材料科学)(英文版)

基　　金：National Key Research and Development Program of China (2021YFC2400500);National Natural Science Foundation of China (52173271, 52361165659, and 52221006);Beijing Outstanding Young Scientist Program(BJJWZYJH01201910010024)。

摘　　要：Post-resection recurrence remains a severe problem in melanoma treatment.New therapeutic strategies,such as chemodynamic therapy(CDT),exhibit high specificity and responsiveness,demonstrating potential to elicit antitumor immune responses by triggering immunogenic cell death(ICD).However,the efficacy of CDT still faces challenges from the immunosuppressive tumor microenvironment(TME)characterized by elevated lactate levels.Herein,we propose a strategy to construct an immunomodulatory hydrogel to synergistically reprogram tumor-associated macrophages and amplify ICD to inhibit melanoma recurrence after surgery.The hyaluronic acid hydrogel containing borosilicate glasses(BGs)and Fe_(3)O_(4) nanoparticles(HBF hydrogel)are obtained,which can neutralize tumor acidity to reprogram macrophages to M1 phenotype.Furthermore,the HBF hydrogel induces reactive oxygen species production in melanoma cells,which could induce ICD through CDT and stimulate strong antitumor immune responses,thereby promoting tumor immunotherapy.The cooperative ICD induced by CDT and immunosuppressive TME remodeling leads to effective suppression of tumor recurrence.This work provides a promising strategy for immunomodulation-enhanced melanoma therapy through the fabrication of hydrogel to prevent postsurgical tumor recurrence.黑色素瘤术后复发仍然是治疗中的一个严重问题.新的治疗策略,如化学动力疗法(CDT),具有高度的特异性和反应性,能够引发免疫原性细胞死亡(ICD),表现出引起抗肿瘤免疫反应的潜力.然而, CDT的疗效被以乳酸水平升高为特征的免疫抑制肿瘤微环境(TME)所抑制.在这里,我们提出了一种使用免疫调节水凝胶重编程肿瘤相关巨噬细胞和诱导ICD以抑制黑色素瘤术后复发的策略.制备了含有硼硅酸盐玻璃和四氧化三铁纳米颗粒的透明质酸水凝胶(HA/BG/Fe-hydrogel,HBF).该水凝胶可中和肿瘤酸性,将TAMs重编程为M1表型.此外, HBF还能产生活性氧,从而通过CDT诱导ICD,激起强烈的抗肿瘤免疫反应,从而增强肿瘤免疫治疗疗效. HBF通过CDT诱导的ICD和逆转免疫抑制TME可有效抑制肿瘤复发.这项工作为构建免疫调节型水凝胶抑制黑色素瘤术后复发提供了一种具有前景的策略.

关 键 词：borosilicate glasses tumor microenvironment chemodynamic therapy tumor acidity melanoma immunotherapy 

分 类 号：R739.5[医药卫生—肿瘤] TQ427.26[医药卫生—临床医学]