Scientists from the Higher Council for Scientific Research (CSIC) have investigated the use of molecular mole cages ’formed by pseudopeptides with the aim of killing cancer cells selectively in acidic microenvironments. The study has been published in the magazine Angewandte Chemie.
The CSIC researchers have analyzed the possibility that the pH of the tumor environment can serve as a selective parameter between healthy cells and malignant cells and, therefore, serve for the design of cancer treatments. Due to the metabolism of cancer cells, the environment around many solid tumors has an acidic pH, which makes them more resistant and capable of metastasizing.
Ignacio Alfonso, a researcher at the CSIC of the Institute of Advanced Chemistry of Catalonia, explained that “a family of amino acid-derived molecules with a cage-shaped three-dimensional structure have been prepared for the study and that, when they are in acidic media, They encapsulate a chloride inside very efficiently. In addition, they are capable of transporting the chloride through lipid bilayers, this transport being also more efficient when there is a pH gradient with an acidic environment ”.
Scientists have achieved these results from the use of different spectroscopic techniques, such as electrochemistry, nuclear magnetic resonance and fluorescence, in simple artificial experimental models, such as micelles and vesicles. Another discovery has been that this concept could be applied in living systems, since the transport through the cell membrane of hydrochloric acid produces adverse effects on the cells, including their death.
Finally, CSIC scientists have demonstrated in human lung adenocarcinoma cells that one of the molecular ‘cages’ was toxic to the cells based on the surrounding pH. In fact, it was five times more toxic if it was with an acidic pH, similar to that in the environment of solid tumors, than with a normal pH of normal cells.
The researcher Ignacio Alfonso has explained that “there is a range of concentrations in which the cage would be safe for cells at pH 7.5, healthy cells, but toxic for those cells that are in a slightly acidic pH, such as the microenvironment of a solid tumor ” These conclusions imply the possibility of extending the use of anionophores, which are negatively charged ion transporters, similar to those used in cancer chemotherapy, using pH as a parameter of selectivity between cancerous and healthy cells.