A Trojan horse to fight cancer by strengthening radiotherapy

A collaboration between RESPORE researchers (ISMO, IMAP, IGPS) has developed a cage nanoparticle allowing a better absorption of the drug Gem-MP and its release in tumor cells. The use of these nanoMOFs would thus improve the effectiveness of radiotherapy.

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A drug that sensitizes tumor cells to radiotherapy, gemcitabine-phosphate monophosphate (Gem-MP) needs to internalize itself into its targets to avoid toxicity in healthy tissues. A collaboration between researchers from ISMO (CNRS/University Paris-Saclay), IMAP (CNRS/ENS Paris/ESPCI Paris) and IGPS (CNRS/University Paris-Saclay) has developed a caged nanoparticle (nanoMOF) capable of absorbing the drug, penetrating tumor cells, and then releasing Gem-MP inside its targets. This work, which made the cover of the ChemMedChem journal, shows that nanoMOFs increase the damage to tumors induced by radiotherapy and that their synergistic action with Gem-MP doubles the effectiveness of radiotherapy.

To destroy cancer cells, radiotherapy ionizes the water present in the tissue to generate highly reactive and toxic radical chemicals, such as hydroxyl radicals. Molecules such as gemcitabine-monophosphate (Gem-MP) sensitize cells to radiation therapy, for example by decreasing their ability to repair themselves. Nanoparticles based on metal-organic frameworks (nanoMOFs) increase the production of hydroxyl radicals after activation by ionizing radiation. Researchers at the Institut des sciences moléculaires d'Orsay (ISMO, CNRS/Université Paris-Saclay), the Institut des matériaux poreux de Paris (IMAP, CNRS/ENS Paris/ESPCI Paris) and the Institut Galien Paris Sud (IGPS, CNRS/Université Paris-Saclay) have therefore used nanoMOFs to develop a real Trojan horse that not only helps the incorporation of the Gem-MP, but itself enhances radiotherapy.

In addition, the porous nanoMOFs function like sponges, absorbing the Gem-MP within their cages. Together they penetrate the membrane of the cancer cells and, once inside, degrade to release the Gem-MP. When an ionizing gamma ray passes over the cells, the synergistic action of the nanoMOFs and the Gem-MP doubles cell mortality. NanoMOFs also have the advantage of not being toxic to healthy cells. These studies pave the way to the design of "all-in-one" nanodrugs where each component plays a role in combating disease.

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