A team of Aragonese scientists discover how to drive a chemical reaction inside tumour cells, capable of destroying key molecules for their proliferation
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A team of scientists from the University of Zaragoza, at the Aragon Nanoscience and Materials Institute (INMA, a joint institute of CSIC and UNIZAR), also attached to CIBER-BBN and IIS Aragon, has discovered how to carry out a new chemical reaction, called transamination, artificially inside cancer cells to destroy molecules of vital importance for the development and growth of tumour cells. The prestigious journal Nano Letters publishes the work led by the University of Zaragoza professors and researchers Javier Bonet-Aletá, José Luis Hueso and Jesús Santamaría, who work at INMA (CSIC-UNIZAR), CIBER-BBN and IIS Aragón.
Catalytic therapy is a new strategy in the fight against cancer, the aim of which is to trigger chemical reactions that are harmful to the tumour. In short, the aim is to replace current chemotherapy by using catalysts that either generate toxic molecules inside the tumour or eliminate molecules that it needs to proliferate.
In this second line of elimination of key molecules, since the first positive results published in 2015, catalysts have targeted either glucose, which is a particularly important source of energy for cancer cells, or glutathione, an antioxidant that protects tumour cells from highly reactive radical species and is partly responsible for the resistance of these cells to chemotherapeutic treatments. Both glucose and glutathione were eliminated by oxidation reactions, which are particularly difficult to apply given the scarcity of oxygen in the hypoxic tumour environment.
This study, published in the prestigious journal Nano Letters, is of particular importance, not only because it opens the field to new reactions of interest in oncology, but also because it does so in a process – transamination – that does not require oxygen to carry out, eliminating the main restriction of catalytic therapies. The reaction operates on amino acids, essential building blocks that cells use to make proteins, and on pyruvate, an abundant small molecule involved in the cell’s main energy-producing pathway. The reaction between the two reduces the levels of amino acid and pyruvate in cancer cells, bringing them to a critical state and slowing their expansion and growth.
During transamination, an amino group is exchanged between an amino acid and pyruvate, generating a substance that the cell is not able to use as easily. Researchers have demonstrated this by reacting pyruvate with different amino acids, such as glutamine, aspartic acid, glutamic acid or glutathione itself. Transamination has a drawback: it is catalysed by copper atoms, whose flow through the cell membrane under normal conditions is severely restricted. To solve this limitation, the researchers designed nanoparticles containing this metal, increasing internalisation into the tumour cell. Once internalised, the nanoparticle dissolves, releasing copper atoms that act as catalysts in the transamination reaction.
The article reports the work led by doctors Javier Bonet Aletá, José Luis Hueso and Jesús Santamaría, teaching and research staff of the University of Zaragoza at the Aragon Nanoscience and Materials Institute (INMA, a joint CSIC-UNIZAR centre), the Biomedical Research Centre Network on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) and the NANBIOSIS Platform and the Institute for Health Research of Aragon (IIS Aragon).
Other members of the University of Zaragoza have also participated, such as Javier Martín Martín Martín, from the Department of Organic Chemistry and INMA, and Miguel Encinas Giménez, Ana Martín Pardillos and Pilar Martín-Duque, also members of the Institute for Health Research (IIS) of Aragón, as well as Dr. Juan Vicente Alegre Requena, CSIC scientist at the Institute of Chemical Synthesis and Homogeneous Catalysis, ISQCH, a joint centre of CSIC and UNIZAR.
Reference:
Nanoparticle-Catalyzed Transamination under Tumor Microenvironment Conditions: A Novel Tool to Disrupt the Pool of Amino Acids and GSSG in Cancer Cells. Javier Bonet Aletá, Juan Vicente Alegre Requena, Javier Martín Martín, Miguel Encinas Giménez, Ana Martín Pardillos, Pilar Martín-Duque, Jose L. Hueso*, and Jesús Santamaría*
Nano Letters, 2024 https://pubs.acs.org/doi/full/10.1021/acs.nanolett.3c04947
08-04-2024
