Endoplasmic-Reticulum targeting compounds for ROS powered chemiluminescent PDT

Brain cancers such as glioblastoma multiforme (GBM) are practically incurable, due to their location, invasiveness, and highly aggressive nature. The use of light-based treatments of glioblastoma multiforme by activating tumor-localized photosensitizers, such as in photodynamic therapy (PDT) has been clinically evaluated, but with limited success. This is mainly due to the limited penetration of light into tissue and the efficient spread of tumor cells typically up to at least 2 cm from the resection margin. Moreover, the existing photon based treatments (photodynamic therapy) are highly invasive and usually require open-cranium surgery, due to the need for external light sources. According to the LUMIBLAST strategy, photons are produced inside the glioblastoma multiforme (GBM) cells in the form of chemiluminescence, avoiding the major limitation of using external light to treat solid, deep-sited and inaccessible tumors. The principle utilized in LUMIBLAST may also be relevant for cancers of other origins. Due to its nature, LUMIBLAST is expected to act on individual cells, rather than the collective lesion; it could thus completely eliminate the hitherto incurable glioblastoma multiforme. Each cancer cell is expected to become a small lamp providing the light required for the photosensitive agents to become activated, killing the tumour cells from the inside. A number of endoplasmic reticulum-targeting, especially-designed compounds were synthesized and used in this regard.