Rational design of mitochondria-targeted fluorescent biosensors for in vivo elucidation of the interaction between breast cancer metastasis and mitochondrial autophagy.

Autor: Yuan L; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China., Cao Y; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China., Zhang Q; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China., Pan J; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China., Wu C; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China., Ye Y; Institute of Pharmaceutical Biotechnology, School of Biology and Food Engineering, Suzhou University, Suzhou, 234000, PR China. Electronic address: yeyaxi666@163.com., Jiao Q; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China. Electronic address: jiaoqc@nju.edu.cn., Zhu HL; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China. Electronic address: zhuhl@nju.edu.cn., Wang Z; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, 210023, PR China. Electronic address: wangzhongchang2006@163.com.
Jazyk: angličtina
Zdroj: Biosensors & bioelectronics [Biosens Bioelectron] 2024 May 01; Vol. 251, pp. 116123. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1016/j.bios.2024.116123
Abstrakt: Breast cancer lung metastases (BCLM) are a major cause of high mortality in patients. The shortage of therapeutic targets and rapid drug screening tools for BCLM is a major challenge at present. Mitochondrial autophagy, which involves the degradation of proteins associated with cancer cell aggressiveness, represents a possible therapeutic approach for the treatment of BCLM. Herein, four fluorescent biosensors with different alkyl chains were designed and synthesized to monitor mitochondrial autophagy. Among them, PMV-12 demonstrated the highest sensitivity to viscosity variance, the least impact on polarity, and the longest imaging time. The introduction of the C 12 -chain made PMV-12 anchored in the mitochondrial membrane without being disturbed by changes of the mitochondrial membrane potential (MMP), thereby achieving the long-term monitor in situ for mitochondrial autophagy. Mitochondria stained with PMV-12 induced swelling and viscosity increase after treating with apigenin, which indicated that apigenin is a potential mitochondrial autophagy inducer. Apigenin was subsequently verified to inhibit cancer cell invasion by 92%. Furthermore, PMV-12 could monitor the process of BCLM in vivo and evaluate the therapeutic effects of apigenin. This work provides a fluorescent tool for elucidating the role of mitochondrial autophagy in the BCLM process and for anti-metastatic drug development.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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