Photoactivated chemotherapy (PACT) enables spatial and temporal precision in research for cancer treatment options. PACT relies on photocleavable protecting groups (PPGs, or photocages) to temporarily inactivate bioactive compounds and enable their controlled release upon light irradiation. In this thesis, the xantheniumderived photocage X590 MMAE was loaded with the chemotherapeutic cargo monomethyl auristatin-E (MMAE), a potent mitotic inhibitor. Its light-triggered release was investigated both in vitro and ex ovo using the chicken chorioallantoic membrane (CAM) model, with activation performed using different light sources such as light emitting diodes (LEDs). In vitro experiments on U87 cell line showed that varying illumination times did not significantly influence the photorelease, due to saturation. Performed IC50 curves indicated that the released MMAE retained full cytotoxicity, whereas the photocage itself was 165-fold less potent. Ex ovo, U87 and Raji tumors were topically treated with X590 MMAE and analyzed histologically, immunohistochemically, and by cell cycle phase distribution using flow cytometry. Quantified results were only obtained by the results provided by flow cytometry. Released MMAE induced mitotic arrest in G2 phase. U87 tumors treated with 50µM X590 MMAE showed the same increase in G2 resting cells as those treated with pure MMAE, when compared to growth control samples, confirming effective light-induced release by LEDs. Focusing the LED beam with a lens setup enhanced photouncaging efficiency by reducing illumination times.
Photocaged drug release: Exploring the phototherapeutic effects of prodrug X590 MMAE in vitro and ex ovo using a cost efficient light source
Pühringer, S. (Author). 2025
Student thesis: Master's Thesis