The article was published in Nature Chemical Biology this week. Building on this work, the team recently received an NWO grant for the PHONIC project – which has started last April – focusing on developing light-responsive drugs for thyroid cancer that can be both activated and monitored by photoacoustic imaging.
Many drugs work well in in vitro models, but cause side effects in patients because they act throughout the body rather than only at the diseased site. This is for example the case in chemotherapy, where organ toxicity and immune suppression often limit treatment. Photopharmacology offers a way around this: drugs are engineered to stay inactive until they are switched on with light, exactly where the disease is located. However, without medical imaging photopharmacology remains blind: therefore, the team envisions a synergy between photopharmacology and molecular to create a theragnostic treatment modality that allows for on-the-fly monitoring of drug activation and its therapeutic effect.
In their Perspective, Szymanski, Vonk, Kruijff and colleagues describe the two main chemical strategies for making drugs light-responsive. Molecular photoswitches reversibly change shape upon irradiation, turning the drug on and off again, while photocages permanently release an active drug from an inactive, “caged” form after a single light pulse. Each strategy is suitable for different clinical situations, ranging from skin conditions treated with topical light to deep tumors that require light delivery during surgery or endoscopy.
A central message of the review is that photopharmacology should not work in isolation. Because many medical imaging techniques, such as X-ray, optical and photoacoustic imaging, and PET, also rely on light or related electromagnetic radiation, they can be used not only to locate disease but also to activate drugs and to verify, in real time, whether therapeutic response has been achieved. The authors describe three levels of this synergy: 1) imaging localizes the disease to guide drug activation or surgery, 2) imaging directly activates the therapy, and 3) imaging probes the successfulness of light activation. The potential of pharmacotherapy is illustrated with two clinical scenarios: a minimally invasive treatment for thyroid nodules guided by photoacoustic imaging, and light-activated antibiotics for infections around joint prostheses.
Building directly on this work, prof. Szymanski and prof. Kruijff, in close collaboration with dr. Vonk, have just been awarded an NWO Open Competition Domain Science grant for the project PHONIC (Pioneering photoacoustic imaging for tumor-specific image-guided photopharmacology). Over the next years, two PhD students will design light-responsive cancer drugs whose distribution and activation can be tracked with photoacoustic imaging, a non-invasive technique that combines light and ultrasound. The project focuses on papillary thyroid carcinoma, where current surgical treatment can cause lifelong side effects despite the disease’s generally excellent prognosis. The aim is a minimally invasive, image-guided alternative that controls the tumor while sparing healthy tissue.
