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

Bonet-Aleta, Javier (Universidad de Zaragoza) ; Alegre-Requena, Juan Vicente ; Martin-Martin, Javier ; Encinas-Gimenez, Miguel (Universidad de Zaragoza) ; Martín-Pardillos, Ana (Universidad de Zaragoza) ; Martin-Duque, Pilar (Universidad de Zaragoza) ; Hueso, Jose L. (Universidad de Zaragoza) ; Santamaria, Jesus (Universidad de Zaragoza)

Resumen: 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 CuFe2O4 nanoparticles are able to foster transaminations with different amino acids and pyruvate, another key molecule present in the TME. We observed a significant in cellulo 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 −NH2 group of GSSG. Our results highlight transamination as alternative to the existing toolbox of catalytic therapies.

Idioma: Inglés

DOI: 10.1021/acs.nanolett.3c04947

Año: 2024

Publicado en: Nano Letters 24, 14 (2024), 4091-4100
ISSN: 1530-6984

Financiación: info:eu-repo/grantAgreement/ES/DGA/E07-23R
Financiación: info:eu-repo/grantAgreement/EC/H2020/742684/EU/Catalytic Dual-Function Devices Against Cancer/CADENCE
Financiación: info:eu-repo/grantAgreement/ES/MICINN/IJC-2020-044217-I

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Estomatología (Dpto. Cirugía)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)