Light-Controlled Drugs: Hungarian Researchers Achieve a Breakthrough in Targeted Therapies

The research focuses on so-called photocages. These are specialised molecules that temporarily inactivate bioactive compounds through a light-cleavable covalent linkage, substantially reducing their biological activity. When exposed to light of an appropriate wavelength suitable for biological applications, this linkage is rapidly cleaved, releasing the active compound at the illuminated site.

The newly developed system is notable in several respects. It is compatible with light sources already used in clinical practice, including 630 nm red light, and is also highly stable in the dark, meaning that the active compound is not released prematurely. The researchers showed that even short periods of illumination are sufficient to trigger release of the active compound.

The effectiveness of the technology is particularly well illustrated by experiments with the potent anticancer agent monomethyl auristatin E (MMAE). This compound is highly toxic even at very low concentrations; however, in its photocaged form, its cytotoxic activity can be reduced by nearly three orders of magnitude. Its full activity can then be restored by localised illumination.

The researchers validated the method at several levels: in conventional cell cultures, in more advanced 3D tumour spheroid models, and in living systems. In collaboration with Austrian partners, they demonstrated in tumours grown on chick embryos that illuminated tumours showed reduced mitotic activity and tumour progression, whereas in the absence of light the effect remained much weaker.

The method is promising not only for anticancer therapies. The researchers also showed that it is suitable for the precise control of rapid biological processes, for example through the light-controlled activation of G protein-coupled receptors. In the longer term, this approach could provide new tools for the selective control of signalling processes relevant to nervous system function.

Although clinical application will require further research, the results represent an important step towards light-activated, targeted drug therapies, particularly chemotherapeutic strategies designed to reduce side effects.

 The full original article is available here: https://doi.org/10.1021/jacs.6c02825