黑色素瘤术后复发是这类疾病在治疗过程中仍然存在的一个严重问题。化学动力学疗法（CDT）等新的治疗策略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，以乳酸水平升高为特征的免疫抑制肿瘤微环境（TME）通常会限制CDT的疗效。
近日，北京化工大学徐福建教授和赵娜娜教授等人在Science China Materials发表研究论文，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。
本文要点
1) 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）。2) 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。3) 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。Figure 1. Schematic of the preparation of HBF hydrogel for antitumor effect through reshaping immunosuppressive TME and triggering immune responses, and the application to prevent post-surgical recurrence of melanoma.Figure 2. Characterization of BGs, Fe3O4 nanoparticles, and HBF hydrogel. (a) SEM image and HRTEM image (inset) of BGs. (b) TEM image and HRTEM image (inset) of Fe3O4 nanoparticles. (c) Hydrodynamic size of Fe3O4 nanoparticles. (d) FTIR spectra of BGs, HA, HA-NH2, and HA-CHO. (e) 1H NMR spectra of HA, HA-NH2 and HA-CHO. (f) SEM image of the HBF hydrogel. (g) Photographs showing the mixing of HA-NH2 containing BGs and HA-CHO containing Fe3O4 nanoparticles to form the HBF hydrogel. (h) Rheological properties of the as-prepared HBF hydrogel measured by the frequency sweep test at a constant strain of 1%. (i) EDS analysis of C, N, Si, and Fe elements in the HBF hydrogel.![]()
Figure 3. Cytotoxicity and immunomodulatory effect of the HBF hydrogels. (a) Viability of L929 cells incubated with HBF hydrogel containing different BG concentrations for 24 h (Mean ± SD, n = 4). (b) Cytotoxicity of HBF hydrogel with different Fe3O4 concentrations in L929 and B16F10 cells after incubation for 24 h (Mean ± SD, n = 4). Representative flow cytometric plots (c) and quantitative analysis (d) of M1- and M2-phenotype macrophages after incubation with different hydrogels (Mean ± SD, n = 3). *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, analyzed by Student’s t-test.![]()
Figure 4. Immune responses of HBF hydrogel-mediated therapy in tumor recurrence model. (a) Lactate levels in tumor tissues after different treatments. Quantification analysis of M1 (b) and M2 (c) macrophages on day 7 after different treatments. (d) Immunofluorescence staining of tumor tissues for CD206 (red) and iNOS (green). (e) Representative flow cytometric plots and quantification of MDSCs in tumors after different treatments. (f) Representative flow cytometric plots and quantification of Tregs in tumors after different treatments. (g) Quantification analysis of matured DCs in TDLNs after different treatments. (h) Quantification analysis of CD8+ T cells in tumors after different treatments. (i) The secretion level of TNF-α in the blood serum. Mean ± SD, n = 3, *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001, analyzed by Student’s t-test.Zhiyuan Quan, Linghui Chen, Beibei Chen, Kangli Guo, Pengfei Tian, Haobo Pan, Yang Li, Nana Zhao, Fu-Jian Xu. Immunomodulatory hydrogel neutralizes tumor acidity to augment immune responses for the prevention of post-surgical recurrence of melanoma. Sci. China Mater. (2024).https://doi.org/10.1007/s40843-024-3176-5
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