Protondynamic therapy: Can protons do the job of light?

Deep lying cancers like the brain cancer glioblastoma multiforme (GBM) are difficult to reach and practically incurable by the current standard-of-care. Even though photosensitive drugs (PSs) are used for fluorescence guided resection of GBM, photomedical treatments like photodynamic therapy (PDT) or photochemical internalisation (PCI) are limited by the depth of light penetration into tissue. Proton radiotherapy, is selective for cancer and can reach deep lying disease. Here we show the results of radical hybridisation of the principles behind PDT and proton therapy. Our hypothesis was that accelerated protons can excite the electrons of PSs, so that the latter can be activated into generating singlet oxygen and thus eliminating cancers like GBM. Indeed, we irradiated PS solutions and gels and verified the PS proton-activation, by fluorescence, i.e. radiative de-excitation of the photosensitive molecules.
Furthermore, we verified the population of PS triplet states in dry gels and finally we registered the production of singlet oxygen, either directly through its characteristic luminescence at 1270 nm or indirectly through the formation of singlet-oxygen-associated photoproducts. Following proof of principle in solutions and gels we proceeded with testing our hypothesis in GBM cell cultures: M059K, T98G and U87, by comparing the survival in cell groups ±PS (cercosporin), irradiated with various proton doses (2-20 Gy). The results revealed increased cell death with the use of PSs in M059K and T98G cells, but not in the U87 cell line.
Twitter: @TheodossisT