An Aggregation-Induced Emission-Based Dual Emitting Nanoprobe for Detecting Intracellular pH and Unravelling Metabolic Variations in Differentiating Lymphocytes.

Autor: Huang Y; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Zhang Q; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Lam CYK; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Li C; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Yang C; Department of Applied Physics, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Zhong Z; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Zhang R; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Yan J; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Chen J; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Yin B; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China.; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Wong SHD; School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.; Laboratory for Marine Drugs and Bioproducts, Qingdao Marine Science and Technology Center, Qingdao 266237, China.; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China.; Research Institute for Sports Science and Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China., Yang M; Department of Biomedical Engineering, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China.; Research Institute for Sports Science and Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong 999077, China.; The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen 518000, China.
Jazyk: angličtina
Zdroj: ACS nano [ACS Nano] 2024 Jun 18; Vol. 18 (24), pp. 15935-15949. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1021/acsnano.4c03796
Abstrakt: Monitoring T lymphocyte differentiation is essential for understanding T cell fate regulation and advancing adoptive T cell immunotherapy. However, current biomarker analysis methods necessitate cell lysis, leading to source depletion. Intracellular pH (pH i ) can be affected by the presence of lactic acid (LA), a metabolic mediator of T cell activity such as glycolysis during T cell activation; therefore, it is a potentially a good biomarker of T cell state. In this work, a dual emitting enhancement-based nanoprobe, namely, AIEgen@F127-AptCD8, was developed to accurately detect the pH i of T cells to "read" the T cell differentiation process. The nanocore of this probe comprises a pair of AIE dyes, TPE-AMC (pH-sensitive moiety) and TPE-TCF, that form a donor-acceptor pair for sensitive detection of pH i by dual emitting enhancement analysis. The nanoprobe exhibits a distinctly sensitive narrow range of pH i values (from 6.0 to 7.4) that can precisely distinguish the differentiated lymphocytes from naïve ones based on their distinct pH i profiles. Activated CD8+ T cells demonstrate lower pH i (6.49 ± 0.09) than the naïve cells (7.26 ± 0.11); Jurkat cells exhibit lower pH i (6.43 ± 0.06) compared to that of nonactivated ones (7.29 ± 0.09) on 7 days post-activation. The glycolytic product profiles in T cells strongly correlate with their pH i profiles, ascertaining the reliability of probing pH i for predicting T cell states. The specificity and dynamic detection capabilities of this nanoprobe make it a promising tool for indirectly and noninvasively monitoring T cell activation and differentiation states.
Databáze: MEDLINE