Genetically engineered probiotics as catalytic glucose depriver for tumor starvation therapy.

Autor:	Ji P; Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, PR China.; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, PR China.; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China., An B; Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.; CAS Key Laboratory of Quantitative Engineering Biology, Materials Synthetic Biology Center, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China., Jie Z; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, PR China.; School of Physical Science and Technology, Shanghai Tech University, Shanghai, 201210, PR China., Wang L; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, PR China.; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China., Qiu S; Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, PR China., Ge C; Center for Materials Synthetic Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.; CAS Key Laboratory of Quantitative Engineering Biology, Materials Synthetic Biology Center, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, PR China., Wu Q; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai, 200081, PR China., Shi J; Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, PR China.; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, PR China.; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China., Huo M; Shanghai Tenth People's Hospital, Shanghai Frontiers Science Center of Nanocatalytic Medicine, School of Medicine, Tongji University, Shanghai, 200072, PR China.; State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics Chinese Academy of Sciences, Research Unit of Nanocatalytic Medicine in Specific Therapy for Serious Disease, Chinese Academy of Medical Sciences (2021RU012), Shanghai, 200050, PR China.; Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Jazyk:	angličtina
Zdroj:	Materials today. Bio [Mater Today Bio] 2022 Dec 15; Vol. 18, pp. 100515. Date of Electronic Publication: 2022 Dec 15 (Print Publication: 2023).
DOI:	10.1016/j.mtbio.2022.100515
Abstrakt:	Cancer cells predominantly adapt the frequent but less efficient glycolytic process to produce ATPs rather than the highly efficient oxidative phosphorylation pathway. Such a regulated metabolic pattern in cancer cells offers promising therapeutic opportunities to kill tumors by glucose depletion or glycolysis blockade. In addition, to guarantee tumor-specific therapeutic targets, effective tumor-homing, accumulation, and retention strategies toward tumor regions should be elaborately designed. In the present work, genetically engineered tumor-targeting microbes (transgenic microorganism EcM-GDH ( Escherichia coli MG1655) expressing exogenous glucose dehydrogenase (GDH) have been constructed to competitively deprive tumors of glucose nutrition for metabolic intervention and starvation therapy. Our results show that the engineered EcM-GDH can effectively deplete glucose and trigger pro-death autophagy and p53-initiated apoptosis in colorectal tumor cells/tissues both in vitro and in vivo . The present design illuminates the promising prospects for genetically engineered microbes in metabolic intervention therapeutics against malignant tumors based on catalytically nutrient deprivation, establishing an attractive probiotic therapeutic strategy with high effectiveness and biocompatibility. Competing Interests: 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. (© 2022 The Authors.)
Databáze:	MEDLINE
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