Target-Selective Phototherapy Using a Ligand-Based Photosensitizer for Type 2 Cannabinoid Receptor

•Development of the CB2 receptor-targeted phototherapy agent, IR700DX-mbc94•IR700DX-mbc94 is only effective when bound to the target receptor•Phototherapeutic effect of IR700DX-mbc94 is much less in CB2R− than in CB2R+ cells•CB2R-targeted phototherapy provides a promising target-specific approach

SummaryPhototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use. Despite the progress and promise, most current phototherapy agents have serious side effects as they can lead to damage to healthy tissue, even when the photosensitizers are fused to targeting molecules due to nonspecific light activation of the unbound photosensitizer. To overcome these limitations, we developed a phototherapy agent that combines a functional ligand and a near infrared phthalocyanine dye. Our target is type 2 cannabinoid receptor (CB2R), considered an attractive therapeutic target for phototherapy given it is overexpressed by many types of cancers that are located at a surface or can be reached by an endoscope. We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (178 K)Download as PowerPoint slide