One of the main issues for modern pharmacology is the inability to control a drug’s activity in space or time after administration, leading to deficient efficacy and the presence of off-target side effects. This is something that the pharmaceutical industry seems to have completely forgotten about – perhaps because a huge proportion of the drug-development dogma revolves around the removal of any drug candidates that are affected by this.
But what if this didn’t need to be the case?
Welcome to the world of photopharmacology – the use of light in controlling the activity of drugs in vivo1.
Light is inarguably one of the most important physical phenomena in the universe. It allows us to identify and see the food we need to eat, and the dangers we need to avoid. It provides the energy with which plants generate the oxygen we need to breathe. It allows us to experience the majestic purple of a summer’s sunset, the delicate blue of a wintry frost, and the deep orange of dying autumnal leaves. It allows us to see our loved ones.
But what you probably didn’t know, is that light may also have a role in the world of medicine. Photopharmacology is a new method of solving some of the oldest problems of modern therapeutics.
The most prominent photopharmacological technique in development is the addition of specific molecular compounds, the structures of which are altered by light2. These so-called ‘photoswitches’, such as azobenzenes, are incorporated into the molecular structure of the drug in question. This allows light to change various properties of the photoswitch-modified drug, such as shape and lipophilicity, which modify the drug’s actions in the body3.
This means that a completely inactive form of a drug (with its photoswitch ‘off’) can be administered, and then activated by a focussed beam of visible light, only when it reaches its target tissue, thus eliminating any off-target side effects that the drug may have otherwise produced4. Additionally, this activation lasts only as long as the drug remains exposed to the beam, meaning no active compounds are introduced into the environment as waste5.
One application of photopharmacology is in chemotherapy. In lay terms, the aim of chemotherapy is to kill cancer cells. One major side effect of this treatment, however, is the destruction of healthy cells, which leads to its long list of severe side effects. The only way that chemotherapeutic agents are able to kill cancer cells, but not healthy cells, is to make them completely selective for the former – perhaps by using photopharmacology. Scientists are currently testing anti-cancer drugs with incorporated ‘photoswitches’, so that they only become activated in the appropriate area (usually a tumour), when light is applied6. The impact this could have on quality-of-life for patients undergoing chemotherapy is an immensely exciting prospect.
Another innovative application of this technology is in antibiotics. As you may be aware, these drugs have an enduring presence in the body and in the environment – both leading to antibiotic resistance, a significant issue in the 21st century. If photopharmacology is applied to the drugs, however, the compounds which remain in the body or the environment will be completely inactive, and will have no long-lasting effect7, solving this problem entirely.
Although this technology is also expected to have applications for other diseases and conditions, such as diabetes, epilepsy and systemic hypertension8, the full breadth of potential usage remains uncertain. What is crystal clear, however, is that photopharmacology is coming – and its overall potential is very bright indeed.
- Borowiak, M., Nahaboo, W., Reynders, M., Nekolla, K., Jalinot, P., Hasserodt, J., Rehberg, M., Delattre, M., Zahler, S., Vollmar, A., Trauner, D. and Thorn-Seshold, O., 2015. Photoswitchable Inhibitors of Microtubule Dynamics Optically Control Mitosis and Cell Death. Cell, 162(2), pp.403-411.
- Fuchter, M., 2020. On the Promise of Photopharmacology Using Photoswitches: A Medicinal Chemist’s Perspective. Journal of Medicinal Chemistry,.
- Szymanski, W., 2020. Szymanski Lab. [online] Szymanski-lab.nl. Available at: http://www.szymanski-lab.nl/Photopharmacology.html
- Hayes, T., 2019. Photopharmacology Offers Light-Controlled Drugs And Therapies. [online] Optics.org. Available at: https://optics.org/news/10/6/29
- Broichhagen, J., Frank, J. and Trauner, D., 2015. A Roadmap to Success in Photopharmacology. Accounts of Chemical Research, 48(7), pp.1947-1960.
- The Economist. 2015. Colourful Chemotherapy. [online] Available at: https://www.economist.com/science-and-technology/2015/07/11/colourful-chemotherapy
- Velema, W., Szymanski, W. and Feringa, B., 2014. Photopharmacology: Beyond Proof of Principle. Journal of the American Chemical Society, 136(6), pp.2178-2191.
- Bregestovski, P. and Zefirov, A., 2019. Optogenetics and photopharmacology – effective tools for managing cell activity using light. Kazan medical journal, 100(1), pp.158-169.