Cancer continues to be one of the main causes of mortality in the world. In Spain it is estimated to reach 279,260 new cases in 2023 (SEOM, Spanish Society of Medical Oncology). Conventional treatments such as chemotherapy or radiotherapy exhibit several drawbacks, especially the lack of specificity and the undesired side effects in patients. In the field of nanobiomedicine, different strategies have recently emerged in an attempt to mitigate this problem, such as photothermal, photodynamic, immunotherapy, chemodynamic or starvation therapy. In addition, the use of nanocatalysts as enzymemimicking surrogates or the combination of heterogeneous catalysts with natural enzymes represents another appealing alternative currently showing promising outcomes towards the treatment of the tumor microenvironment (TME). For this purpose, magnetite NPs coated with polyethylenimine, PEI, have been synthesized, providing them with a positive charge at physiological pH and being able to adsorb enzymes whose isoelectric point is lower than this pH. Thus, Glucose Oxidase (GOx) and Catalase have been adsorbed independently, adsorbing 0.68 mg/mg of Fe3O4 and 0.56 mg/mg of Fe3O4, respectively. The interest of these enzymes lies in the fact that GOx may eliminate the glucose necessary for the energy supply of the cell and simultaneously generate H2O2. Likewise, catalase can supply the oxygen necessary for GOx to maintain its activity that is normally hindered under the hypoxic conditions of the TME. Additional catalytic tests have confirmed the rapid and effective consumption of glucose and the additional generation of oxygen induced by the enzymes. At low concentrations (around 0.008 mg/mL of Fe3O4) they prove to be subcytotoxic in cancer cell lines U251 (Human malignant glioblastoma) and HeLa (cervical-uterine cancer), being able to internalize in these cells as shown by confocal microscopy images (Fig. 1-A, 1-B). In addition, by Microwave Plasma Atomic Emission Spectroscopy (MP-AES) we have quantified the total Fe inside the cells, thus confirming internalization.

Resumen del trabajo presentado a la XXXIX Reunión Bienal de la Real Sociedad Española de Química, celebrada en Zaragoza del 25 al 29 de junio de 2024.

This research has been funded through the EU ERC Advanced Grant CADENCE nº GA 742684.

Peer reviewed