Unraveling the Photochemistry of Radiosensitizers and Radioprotectors in Free Biomolecular Complexes

Dramatically increasing cancer cases around the world call for extra research efforts to improve cancer therapies. Radiation therapy or radiotherapy is one of the most common treatment methods. A way to enhance radiotherapy is inserting radiosensitizers (RSs) and radioprotectors (RPs) into the patients body. RSs in tumor cells make them more sensitive to radiation damage, allowing one to use reduced radiation doses, thus minimizing side effects. In contrast, RPs inhibit the damage of healthy cells from radiation. RSs and RPs are actively studied mostly in clinical trials. However, the fundamental mechanisms causing damage or death of cancer cells are not fully understood. Therefore, this project aims at elucidating the elementary steps of radiation damage, their enhancement by RSs, and their inhibition by RPs. The technique combines beams of mixed molecular clusters and doped helium nanodroplets uniquely with synchrotron spectroscopy, electron spectroscopy, and ion mass spectrometry. The main goals are to unravel the photochemistry of selected organic RS compounds (nimorazole, NIMO, bromoadenine, WR-1065 dihydrochloride), metal ions (Mg2+, Ca2+, K+), and gold (RS) and silver (RP) nanoparticles in the state of controlled microhydration and contact with DNA components (thymine, cytosine, tetrahydrofuran). Emission of slow electrons, water fragmentation, and anions formation are observables for radiation damage enhanced by RSs. A time-resolved experiment on the tetrahydrofuran-water complex will elucidate the ultrafast dynamics of intermolecular energy transfer causing dissociation, a mechanism recently identified to play an important role in radiation damage. A better understanding of the radiochemistry of RPs and RSs obtained with this project may help develop new schemes for efficient cancer treatment and identify new types of molecules or nanoparticles with improved RS or RP properties.