Shi Changrong, Zhang Qianyu, Yao Yuying, Zeng Fantian, Du Chao, Nijiati Sureya, Wen Xuejun, Zhang Xinyi, Yang Hongzhang, Chen Haoting, Guo Zhide, Zhang Xianzhong, Gao Jinhao, Guo Weisheng, Chen Xiaoyuan, Zhou Zijian
State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine, Department of Laboratory Medicine, School of Public Health, Xiamen University, Xiamen, China.
Department of Minimally Invasive Interventional Radiology, State Key Laboratory of Respiratory Disease, School of Biomedical Engineering & the Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Nat Nanotechnol. 2023 Jan;18(1):86-97. doi: 10.1038/s41565-022-01261-7. Epub 2022 Dec 19.
T cells play a determining role in the immunomodulation and prognostic evaluation of cancer treatments relying on immune activation. While specific biomarkers determine the population and distribution of T cells in tumours, the in situ activity of T cells is less studied. Here we designed T-cell-targeting fusogenic liposomes to regulate and quantify the activity of T cells by exploiting their surface redox status as a chemical target. The T-cell-targeting fusogenic liposomes equipped with 2,2,6,6-tetramethylpiperidine (TEMP) groups neutralize reactive oxygen species protecting T cells from oxidation-induced loss of activity. Meanwhile, the production of paramagnetic 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) radicals allows magnetic resonance imaging quantification of the T cell activity. In multiple mouse models, the T-cell-targeting fusogenic liposomes led to efficient tumour inhibition and to early prediction of radiotherapy outcomes. This study uses a chemical targeting strategy to measure the in situ activity of T cells for cancer theranostics and may provide further understanding on engineering T cells for cancer treatment.
T细胞在依赖免疫激活的癌症治疗的免疫调节和预后评估中起着决定性作用。虽然特定生物标志物决定了肿瘤中T细胞的数量和分布，但对T细胞的原位活性研究较少。在此，我们设计了靶向T细胞的融合脂质体，通过利用其表面氧化还原状态作为化学靶点来调节和量化T细胞的活性。配备2,2,6,6-四甲基哌啶（TEMP）基团的靶向T细胞的融合脂质体可中和活性氧，保护T细胞免受氧化诱导的活性丧失。同时，顺磁性2,2,6,6-四甲基哌啶1-氧基（TEMPO）自由基的产生使磁共振成像能够对T细胞活性进行量化。在多个小鼠模型中，靶向T细胞的融合脂质体导致有效的肿瘤抑制并能早期预测放疗结果。本研究采用化学靶向策略来测量T细胞的原位活性用于癌症诊疗，可能会为癌症治疗中工程化T细胞提供进一步的理解。
