Yalamandala Bhanu Nirosha, Moorthy Thrinayan, Liu Zhuo-Hao, Huynh Thi My Hue, Iao Hoi Man, Pan Wan-Chi, Wang Kang-Li, Chiang Chi-Shiun, Chiang Wen-Hsuan, Liao Lun-De, Liu Yu-Chen, Hu Shang-Hsiu
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, 300044, Taiwan.
Department of Neurosurgery, Chang Gung Memorial Hospital, Taoyuan, 33305, Taiwan.
Small. 2025 Feb;21(5):e2406178. doi: 10.1002/smll.202406178. Epub 2024 Dec 15.
The recruitment of T lymphocytes holds great potential for suppressing the most aggressive glioblastoma (GBM) recurrence with immunotherapy. However, the phenomenon of immune privilege and the generally low immunogenicity of vaccines often reduce the presence of lymphocytes within brain tumors, especially in brain tumor recurrence clusters. In this study, an implantable self-cascading catalytic therapy and antigen capture scaffold (CAS) that can boost catalytic therapy efficiency at post-surgery brain tumor and capture the antigens via urethane-polyethylene glycol-polypropylene glycol (PU-EO-PO) segments are developed for postoperative brain immunotherapy. The CAS consists of 3D-printed elastomers modified with iron (Fe) metal-organic frameworks (MOFs, MIL88) and acts as a programmed peroxide mimic in cancer cells to initiate the Fenton reaction and sustain ROS production. With the assistance of chloroquine (CQ), autophagy is inhibited through lysosome deacidification, which interrupts the self-defense mechanism, further enhances cytotoxicity, and releases antigens. Then, CAS containing PU-EO-PO groups acts as an antigen depot to detain autologous tumor-associated antigens to dendritic cells maturation and T cell augments for sustained immune stimulation. CAS enhanced the immune response to postoperative brain tumors and improved survival through brain immunotherapy.
招募T淋巴细胞在通过免疫疗法抑制最具侵袭性的胶质母细胞瘤（GBM）复发方面具有巨大潜力。然而，免疫豁免现象以及疫苗通常较低的免疫原性常常会减少脑肿瘤内淋巴细胞的存在，尤其是在脑肿瘤复发簇中。在本研究中，开发了一种可植入的自级联催化疗法和抗原捕获支架（CAS），其能够提高术后脑肿瘤的催化治疗效率，并通过聚氨酯 - 聚乙二醇 - 聚丙二醇（PU-EO-PO）片段捕获抗原，用于术后脑免疫治疗。CAS由用铁（Fe）金属有机框架（MOF，MIL88）修饰的3D打印弹性体制成，在癌细胞中充当程序化的过氧化物模拟物，引发芬顿反应并持续产生ROS。在氯喹（CQ）的协助下，通过溶酶体去酸化抑制自噬，这会中断自我防御机制，进一步增强细胞毒性并释放抗原。然后，含有PU-EO-PO基团的CAS充当抗原库，扣留自体肿瘤相关抗原以促进树突状细胞成熟和T细胞扩增，从而实现持续的免疫刺激。CAS通过脑免疫疗法增强了对术后脑肿瘤的免疫反应并改善了生存率。
