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Photocontrolled Chemotherapeutics (completed)

In vivo anticancer applications of photoswitchable antimitotics (completed project CytoSwitch)

Photoswitchable bioactives hold potential for tissue-localised bioactivity targeting in vivo, as controlled by tissue-localised illumination. Local administration of photoswitchable compounds to photocontrol excitable cells has been used for over a decade in neuroscience. However, the question remains open, of whether photoswitchable therapeutics can advance towards clinical development, for which they will require systemic administration coupled with local photoactivation (by fibre optic, LED implant, etc). Particularly, such therapeutics would be desirable for pathologies that are tissue-localised, yet poorly-treatable with current drugs due to systemic side-effects. Non-resectable solid tumours are one such class of pathology. Their treatment with cytotoxic chemotherapeutics like paclitaxel, doxorubicin or cisplatin is associated with strong systemic side-effects. Weaker patient populations (children, the elderly, those with pre-existing medical conditions) are often unable to tolerate such side-effects and may not be able to receive treatment; and even stronger patients may only be able to tolerate drug dosages that are insufficient to ensure cancer eradication.

From 2015-2020 we researched the potential of photoswitchable antimitotics to be employed in long-term systemic application as tumour-localisable cancer therapeutics in adult mouse models, as the CytoSwitch translational project (funded by an EXIST-Forschungstransfer grant of the BMWi, and the Bavarian FLÜGGE program). We trialled our photoswitchable tubulin inhibitors PST-1P and PST-2S in mouse tumour models as mechanistically defined chemotherapeutics that can be targeted precisely to tumours by local activation with light, thereby sparing healthy tissues from side-effects. The project work covered electronics, light delivery optics, medicinal chemistry, and tumour biology, to experimentally assess the requirements for successful photopharmaceutical drugs directly in murine cancer models. This involves balancing parameters such as wavelength response, activated-state halflife, and drug as well as photoswitch scaffold ADME-PK/PD, to test novel classes of cancer chemotherapy candidates.

Results will be published from 2022.