» Articles » PMID: 38489158

Nanoparticle-Catalyzed Transamination Under Tumor Microenvironment Conditions: A Novel Tool to Disrupt the Pool of Amino Acids and GSSG in Cancer Cells

Overview
Journal Nano Lett
Specialty Biotechnology
Date 2024 Mar 15
PMID 38489158
Authors
Affiliations
Soon will be listed here.
Abstract

Catalytic cancer therapy targets cancer cells by exploiting the specific characteristics of the tumor microenvironment (TME). TME-based catalytic strategies rely on the use of molecules already present in the TME. Amino groups seem to be a suitable target, given the abundance of proteins and peptides in biological environments. Here we show that catalytic CuFeO nanoparticles are able to foster transaminations with different amino acids and pyruvate, another key molecule present in the TME. We observed a significant decrease in glutamine and alanine levels up to 48 h after treatment. In addition, we found that di- and tripeptides also undergo catalytic transamination, thereby extending the range of the effects to other molecules such as glutathione disulfide (GSSG). Mechanistic calculations for GSSG transamination revealed the formation of an imine between the oxo group of pyruvate and the free -NH group of GSSG. Our results highlight transamination as alternative to the existing toolbox of catalytic therapies.

References
1.
Chen S, Yang J, Liang Z, Li Z, Xiong W, Fan Q . Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System. ACS Appl Mater Interfaces. 2023; 15(2):2705-2713. DOI: 10.1021/acsami.2c19585. View

2.
KREBS H . The effect of inorganic salts on the ketone decomposition of oxaloacetic acid. Biochem J. 1942; 36(3-4):303-5. PMC: 1265695. DOI: 10.1042/bj0360303. View

3.
Chai J, Head-Gordon M . Long-range corrected hybrid density functionals with damped atom-atom dispersion corrections. Phys Chem Chem Phys. 2008; 10(44):6615-20. DOI: 10.1039/b810189b. View

4.
Perez-Lopez A, Rubio-Ruiz B, Sebastian V, Hamilton L, Adam C, Bray T . Gold-Triggered Uncaging Chemistry in Living Systems. Angew Chem Int Ed Engl. 2017; 56(41):12548-12552. PMC: 5655737. DOI: 10.1002/anie.201705609. View

5.
Wang Z, Li N, Zhao J, White J, Qu P, Xing B . CuO nanoparticle interaction with human epithelial cells: cellular uptake, location, export, and genotoxicity. Chem Res Toxicol. 2012; 25(7):1512-21. DOI: 10.1021/tx3002093. View