A Multifunctional Molecular Probe for Multimodal Imaging‐Guided Potent Photothermal/Photodynamic Therapy of Endometriosis

Abstract Multifunctional small‐molecule theranostic agents hold significant clinical potential for non‐invasive endometriosis (EMS) management. Current EMS treatment faces challenges due to imprecise lesion localization and therapy‐associated side effects. Herein, an integrated theranostic probe, cRGDyK‐ICG‐Lys‐DTPA@Gd (cRGD‐ILD), designed for concurrent precise lesion localization and targeted phototherapy in EMS, is developed. This molecular probe integrates three key functional components: the DTPA@Gd complex provides contrast for magnetic resonance imaging, the ICG fragment enables fluorescence imaging and photoacoustic imaging while serving as the phototherapeutic agent, and the cRGD peptide targets integrin α v β 3 receptors to facilitate precise accumulation in ectopic endometrial tissue. Specifically, cRGD‐ILD leverages its small size and receptor‐mediated transcytosis to penetrate neovascularized tissue and target ectopic endometrial cells. Under 808 nm laser irradiation, the ICG moiety generates reactive oxygen species and heat, exerting combined photodynamic and photothermal therapeutic effects that effectively suppress lesion progression in both autografted EMS rats and xenografted nude mice. Notably, composed of clinically available and FDA‐approved constituents, the probe demonstrates favorable biocompatibility and biosafety for in vivo applications. Overall, this well‐designed molecular probe enables precise multimodal imaging guidance and localized phototherapy for EMS.