1. Academic Validation
  2. Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics

Targeting the activity of T cells by membrane surface redox regulation for cancer theranostics

  • Nat Nanotechnol. 2022 Dec 19. doi: 10.1038/s41565-022-01261-7.
Changrong Shi # 1 Qianyu Zhang # 1 Yuying Yao 2 Fantian Zeng 1 Chao Du 1 Sureya Nijiati 1 Xuejun Wen 1 Xinyi Zhang 1 Hongzhang Yang 1 Haoting Chen 2 Zhide Guo 1 Xianzhong Zhang 1 Jinhao Gao 3 Weisheng Guo 4 Xiaoyuan Chen 5 6 7 8 Zijian Zhou 9
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 State Key Laboratory of Physical Chemistry of Solid Surfaces & The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, China.
  • 4 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. [email protected]
  • 5 Departments of Diagnostic Radiology, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore. [email protected]
  • 6 Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected]
  • 7 Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore. [email protected]
  • 8 Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore. [email protected]
  • 9 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. [email protected]
  • # Contributed equally.
Abstract

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.

Figures
Products