AI Chat Paper
Discover the SciOpen Platform and Achieve Your Research Goals with Ease.
Search articles, authors, keywords, DOl and etc.
{{expandStatus?'Exit ':''}}Advanced Search
Dual inhibition of glycolysis and oxidative phosphorylation (OXPHOS) can break the metabolic plasticity of cancer cells to inhibit most energy supply and lead to effective cancer therapy. However, the pharmacokinetic difference among drugs hinders these two inhibitions to realize a uniform temporal and spatial distribution. Herein, we report an aptamer-based artificial enzyme for simultaneous dual inhibition of glycolysis and OXPHOS, which is constructed by arginine aptamer modified carbon-dots-doped graphitic carbon nitride (AptCCN). AptCCN can circularly capture intracellular arginine attribute to the specific binding ability of arginine aptamers to arginine, and further catalyze the oxidation of enriched arginine to nitric oxide (NO) under red light irradiation. In vitro and in vivo experiments showed that arginine depletion and NO stress could inhibit glycolysis and OXPHOS, leading to energy blockage and apoptosis of cancer cells. The presented aptamer-based artificial enzyme strategy provides a new path for cell pathway regulation and synergistic cancer therapy.
DeBerardinis, R. J.; Lum, J. J.; Hatzivassiliou, G.; Thompson, C. B. The biology of cancer: Metabolic reprogramming fuels cell growth and proliferation. Cell Metab. 2008, 7, 11–20.
Eisenberg, L.; Eisenberg-Bord, M.; Eisenberg-Lerner, A.; Sagi-Eisenberg, R. Metabolic alterations in the tumor microenvironment and their role in oncogenesis. Cancer Lett. 2020, 484, 65–71.
Faubert, B.; Solmonson, A.; DeBerardinis, R. J. Metabolic reprogramming and cancer progression. Science 2020, 368, eaaw5473.
Nagao, A.; Kobayashi, M.; Koyasu, S.; Chow, C. C. T.; Harada, H. HIF-1-dependent reprogramming of glucose metabolic pathway of cancer cells and its therapeutic significance. Int. J. Mol. Sci. 2019, 20, 238.
Panigrahi, D. P.; Praharaj, P. P.; Bhol, C. S.; Mahapatra, K. K.; Patra, S.; Behera, B. P.; Mishra, S. R.; Bhutia, S. K. The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics. Semin. Cancer Biol. 2020, 66, 45–58.
Lin, Y. H.; Satani, N.; Hammoudi, N.; Yan, V. C.; Barekatain, Y.; Khadka, S.; Ackroyd, J. J.; Georgiou, D. K.; Pham, C. D.; Arthur, K. et al. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers. Nat. Metab. 2020, 2, 1413–1426.
Roth, K. G.; Mambetsariev, I.; Kulkarni, P.; Salgia, R. The mitochondrion as an emerging therapeutic target in cancer. Trends Mol. Med. 2020, 26, 119–134.
Ashton, T. M.; McKenna, W. G.; Kunz-Schughart, L.; Higgins, G. S. Oxidative phosphorylation as an emerging target in cancer therapy. Clin. Cancer Res. 2018, 24, 2482–2490.
Jia, D. Y.; Park, J. H.; Jung, K. H.; Levine, H.; Kaipparettu, B. A. Elucidating the metabolic plasticity of cancer: Mitochondrial reprogramming and hybrid metabolic states. Cells 2018, 7, 21.
Jia, D. Y.; Lu, M. Y.; Jung, K. H.; Park, J. H.; Yu, L. L.; Onuchic, J. N.; Kaipparettu, B. A.; Levine, H. Elucidating cancer metabolic plasticity by coupling gene regulation with metabolic pathways. Proc. Natl. Acad. Sci. USA 2019, 116, 3909–3918.
Li, T.; Han, J. B.; Jia, L. J.; Hu, X.; Chen, L. Q.; Wang, Y. G. PKM2 coordinates glycolysis with mitochondrial fusion and oxidative phosphorylation. Protein Cell 2019, 10, 583–594.
Oshima, N.; Ishida, R.; Kishimoto, S.; Beebe, K.; Brender, J. R.; Yamamoto, K.; Urban, D.; Rai, G.; Johnson, M.; Benavides, G. et al. Dynamic imaging of LDH inhibition in tumors reveals rapid in vivo metabolic rewiring and vulnerability to combination therapy. Cell Rep. 2020, 30, 1798–1810.e4.
Shiratori, R.; Furuichi, K.; Yamaguchi, M.; Miyazaki, N.; Aoki, H.; Chibana, H.; Ito, K.; Aoki, S. Glycolytic suppression dramatically changes the intracellular metabolic profile of multiple cancer cell lines in a mitochondrial metabolism-dependent manner. Sci. Rep. 2019, 9, 18699.
Hu, C. M. J.; Zhang, L. F. Nanoparticle-based combination therapy toward overcoming drug resistance in cancer. Biochem. Pharmacol. 2012, 83, 1104–1111.
Kremer, J. C.; Prudner, B. C.; Lange, S. E. S.; Bean, G. R.; Schultze, M. B.; Brashears, C. B.; Radyk, M. D.; Redlich, N.; Tzeng, S. C.; Kami, K. et al. Arginine deprivation inhibits the Warburg effect and upregulates glutamine anaplerosis and serine biosynthesis in ASS1-deficient cancers. Cell Rep. 2017, 18, 991–1004.
Jahani, M.; Noroznezhad, F.; Mansouri, K. Arginine: Challenges and opportunities of this two-faced molecule in cancer therapy. Biomed. Pharmacother. 2018, 102, 594–601.
Zheng, D. W.; Li, B.; Li, C. X.; Xu, L.; Fan, J. X.; Lei, Q.; Zhang, X. Z. Photocatalyzing CO2 to CO for enhanced cancer therapy. Adv. Mater. 2017, 29, 1703822.
Liu, J.; Liu, Y.; Liu, N. Y.; Han, Y. Z.; Zhang, X.; Huang, H.; Lifshitz, Y.; Lee, S. T.; Zhong, J.; Kang, Z. H. Metal-free efficient photocatalyst for stable visible water splitting via a two-electron pathway. Science 2015, 347, aaa3145.
Fang, X.; Cai, S. X.; Wang, M.; Chen, Z. W.; Lu, C. H.; Yang, H. H. Photogenerated holes mediated nitric oxide production for hypoxic tumor treatment. Angew. Chem., Int. Ed. 2021, 60, 7046–7050.
Zheng, D. W.; Chen, Y.; Li, Z. H.; Xu, L.; Li, C. X.; Li, B.; Fan, J. X.; Cheng, S. X.; Zhang, X. Z. Optically-controlled bacterial metabolite for cancer therapy. Nat. Commun. 2018, 9, 1680.
Zhou, H. X.; Rivas, G.; Minton, A. P. Macromolecular crowding and confinement: Biochemical, biophysical, and potential physiological consequences. Annu. Rev. Biophys. 2008, 37, 375–397.
Ellis, R. J. Macromolecular crowding: An important but neglected aspect of the intracellular environment. Curr. Opin. Struct. Biol. 2001, 11, 114–119.
Rabinovich, S.; Adler, L.; Yizhak, K.; Sarver, A.; Silberman, A.; Agron, S.; Stettner, N.; Sun, Q.; Brandis, A.; Helbling, D. et al. Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis. Nature 2015, 527, 379–383.
Dillon, B. J.; Prieto, V. G.; Curley, S. A.; Ensor, C. M.; Holtsberg, F. W.; Bomalaski, J. S.; Clark, M. A. Incidence and distribution of argininosuccinate synthetase deficiency in human cancers: A method for identifying cancers sensitive to arginine deprivation. Cancer 2004, 100, 826–833.
Pavlova, N. N.; Thompson, C. B. The emerging hallmarks of cancer metabolism. Cell Metab. 2016, 23, 27–47.
Amin, S.; Yang, P.; Li, Z. Y. Pyruvate kinase M2: A multifarious enzyme in non-canonical localization to promote cancer progression. BBA—Rev. Cancer 2019, 1871, 331–341.
Carpenter, A. W.; Schoenfisch, M. H. Nitric oxide release: Part II. Therapeutic applications. Chem. Soc. Rev. 2012, 41, 3742–3752.
Xu, J. S.; Zeng, F.; Wu, H.; Hu, C. P.; Yu, C. M.; Wu, S. Z. Preparation of a mitochondria-targeted and NO-releasing nanoplatform and its enhanced pro-apoptotic effect on cancer cells. Small 2014, 10, 3750–3760.
Xiang, Q.; Qiao, B.; Luo, Y. L.; Cao, J.; Fan, K.; Hu, X. H.; Hao, L.; Cao, Y.; Zhang, Q. X.; Wang, Z. G. Increased photodynamic therapy sensitization in tumors using a nitric oxide-based nanoplatform with ATP-production blocking capability. Theranostics 2021, 11, 1953–1969.
京公网安备11010802044758号