中国科学院精密测量科学与技术创新研究院陈世桢团队报道，通过¹²⁹Xe MRI监测基于Fe₃O₄的纳米颗粒介导的ROS响应性铁中毒和免疫治疗。相关研究成果发表在2024年3月29日出版的国际学术期刊《德国应用化学》。

免疫检查点阻断策略提高了晚期癌症患者的生存率。然而，低免疫应答率限制了免疫治疗的效率。

该文中，研究人员报道了一种ROS响应性的Fe₃O₄基纳米颗粒，它在肿瘤微环境中经历电荷逆转和分解，增强肿瘤细胞对Fe₃O₄的摄取，并引发更严重的脱铁症。在肿瘤微环境中，纳米颗粒在过表达的H₂O₂下快速分解并释放负载的GOx和免疫激活肽Tuftsin。GOx可以消耗肿瘤细胞的葡萄糖并产生更多的H₂O₂，促进纳米颗粒的分解和药物释放，从而增强脱铁性贫血的治疗效果。

与Tuftsin结合，可以更有效地逆转免疫抑制微环境，促进肿瘤组织中效应T细胞的聚集。最终，与α-PD-L1联合使用，可以显著抑制肺转移瘤的生长。此外，超极化¹²⁹Xe方法已用于评估Fe₃O₄纳米粒子介导的免疫疗法，其中肺转移瘤的通气缺陷已得到显著改善，肺结构和功能已完全恢复。铁蛋白增强免疫疗法结合非辐射评估方法，为癌症治疗设计新的治疗剂开辟了新的途径。

附：英文原文

Title: Monitoring ROS Responsive Fe3O4-based Nanoparticle Mediated Ferroptosis&Immunotherapy via 129Xe MRI

Author: Lei Zhang, Maosong Qiu, Ruifang Wang, Sha Li, Xiaoxun Liu, Qiuyi Xu, Long Xiao, Zhong-Xing Jiang, Xin Zhou, Shizhen Chen

Issue&Volume: 2024-03-29

Abstract: The immune checkpoint blockade strategy has improved the survival rate of late-stage lung cancer patients. However, the low immune response rate limits the immunotherapy efficiency. Here, we report a ROS-responsive Fe3O4-based nanoparticle that undergoes charge reversal and disassembly in the tumor microenvironment, enhancing the uptake of Fe3O4 by tumor cells and triggering a more severe ferroptosis. In the tumor microenvironment, the nanoparticle rapidly disassembles and releases the loaded GOx and the immune-activating peptide Tuftsin under overexpressed H2O2. GOx can consume the glucose of tumor cells and generate more H2O2, promoting the disassembly of the nanoparticle and drug release, thereby enhancing the therapeutic effect of ferroptosis. Combined with Tuftsin, it can more effectively reverse the immune-suppressive microenvironment and promote the recruitment of effector T cells in tumor tissues. Ultimately, in combination with α-PD-L1, there is significant inhibition of the growth of lung metastases. Additionally, the hyperpolarized 129Xe method has been used to evaluate the Fe3O4 nanoparticle-mediated immunotherapy, where the ventilation defects in lung metastases have been significantly improved with complete lung structure and function recovered. The ferroptosis-enhanced immunotherapy combined with non-radiation evaluation methodology paves a new way for designing novel theranostic agents for cancer therapy.

DOI: 10.1002/anie.202403771

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202403771