Spatiotemporal Control of Inflammation via Light-Responsive Anti-Inflammatory Agents

Inflammation is a fundamental defence mechanism of the human body, helping to fight infections and repair tissue damage. However, when the inflammatory response is not properly resolved, it can turn harmful, leading to chronic inflammation. This destructive ending phase can be the responsible for many degenerative diseases, autoimmune disorders, and even cancer. A key player in this process is the enzyme cyclooxygenase-2 (COX-2). It regulates the production of pro-inflammatory lipid mediators such as prostaglandins (e.g. PGE2), which can contribute to tumour progression by helping on the development of the tumour microenvironment (TME). While COX-2 selective inhibitors (known as coxibs) have proven effectiveness in reducing inflammation and preventing disease progression, their widespread use is limited due to significant gastrointestinal and cardiovascular side effects. In this work, we present a new approach to anti-inflammatory therapy using light-induced derivatives of celecoxib (a known coxib). By combining computational modelling (in silico), laboratory experiments (in vitro), and animal studies (in vivo), we demonstrate that these photoactivatable compounds allow precise control over the timing and location of drug activity. Our results highlight the potential use of these compounds as next-generation therapeutics to control inflammation. These new photoswitches are offering safer and more targeted treatment options for patients with cancer and other inflammation-related diseases. This study highlights the potential of photopharmacology to transform anti-inflammatory therapies. Our results provide a proof of concept that light-controlled modulation of inflammation is feasible and effective, opening the door to safer and more precise clinical treatments.