What is Photopharmacology?
Photopharmacology is a rapidly emerging field in medicine to develop synthetic drugs that can be activated by light. Due to high spatiotemporal precision, the approach can be used for target drug delivery.
In principal, clinicians use the energy of light to locally activate a previously applied prodrug, thus changing its chemical properties, resulting in biological activity. There are different modes of action currently used in photopharmacology, namely photodynamic therapy, photo-uncaging and photoswitching.
Photodynamic Therapy - Fighting Cancer
Photodynamic therapy is a popular application of photopharmacology. It is a medical treatment using light and a chemical photosensitizer in conjunction with molecular oxygen to produce reactive oxygen species (ROS) and radicals, leading to cell death. It is most commonly used to locally destroy diseased cells and tissue in conditions and diseases such as acne, psoriasis, age-related macular degeneration as well as certain cancers. Selectivity is achieved by the preferential accumulation of the photosensitizer in the diseased tissue and the localized illumination of the area to be treated.
First generation photosensitizers, such as Photofrin, exhibited the disadvantage of prolonged photosensitivity in patients. This negative side effect could be largely overcome by the development of second generation photosensitizers, such as Verteporfin, and third generation antibody-directed photosensitizers. These novel prodrugs have the advantage of a much faster clearance rate, thus minimizing the unwanted effect of patient skin photosensitivity.
Nowadays, photosensitizers in photopharmacology also find application in other fields like the sterilization of blood plasma and wastewater treatment in order to remove viruses and microbes. Antibacterial photodynamic therapy might prove to be a promising strategy in effectively fighting multidrug-resistant pathogenic bacteria without the risk of antimicrobial resistance (AMR).
Unleashing Effectors via Photo-uncaging
Another commonly used approach in photopharmacology is the photo-uncaging of small molecules or chemical compounds. Photostimulation of the caged compound leads to photolysis of the shielding cage molecule. The uncaged core compound then becomes biochemically active, binding to a downstream effector. Depending on the nature of the caged compound, the biological outcome after photostimulation can either be inhibitory or have an activating effect.
Apart from the use as prodrug, caged compounds such as commercially available caged neurotransmitters can be used to study action potential firing with high spatiotemporal precision. When combined with a reporter molecule such as a caged fluorophore, these small molecules allow the detection of biological activity at specific timepoints after application.
Photoswitching - Light-reversible Pharmacological Activity
A widely used optically active tool in photopharmacology is a photoswitch. A photoswitch is a molecule that reversibly changes its chemical and/or optical properties upon light irradiation. Illumination with a certain wavelength leads to photoisomerization of the molecule into its active state, whereas light of a second wavelength relaxes the molecule back into its inactive ground state. Synthetic photoswitches such as azobenzene derivatives have previously been used to probe the kinetics of for example nicotinic receptors. This is made possible by the different pharmacological binding properties of the cis and trans stereoisomers of the molecule, respectively.
Apart from probing the activity of receptors, synthetic photoswitches can also be used to reversibly and remotely control a drug's activity with high temporal precision at the desired site of action with a simple flash of light.
Up until now, photoswitching of pharmacologically active compounds has been applied to target not only transmembrane proteins (e.g. transporters, ion channels, G protein-coupled receptors) and soluble proteins (e.g. kinases, proteases), but also lipid membranes and even nucleic acids.
An impressive application of a newly developed benzimidazole photoswitch (OptoBI-1) has been achieved by our pxONE user family member Bernadett Bacsa and the team of Prof. Klaus Groschner. They accomplished fully light-reversible pharmacological control over the activity of the TRPC3 channel in T-lymphocytes.
LED Illumination for Photopharmacology
To regulate photopharmacologically active tools (and all other optically controlled substances), they need to be illuminated with a specific wavelength. Although wavelength specific illumination devices are available (LED-flashlights etc.) they are often not suited for a particular experimental approach. We at opto biolabs develop illumination devices suited to your experimental approach. Have a look in our product section and find the right illumination device for your photopharmacologic experiment. Do not hesitate to contact us if you cannot find a suitable solution. We build customized illumination devices tailored to your problem.
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For more background and in-depth information check out our publications area to find some reviews for easy reading and some exciting papers.