A photoconvertible Chenopodium album water-soluble-chlorophyll-binding protein as a contrast agent for photoacoustic imaging

Photoacoustic (PA) imaging is a non-invasive modality that combines high spatial resolution with real-time molecular visualization. The development of contrast agents with high sensitivity, deep tissue penetration, and specificity remains a critical challenge. Water-Soluble chlorophyll-binding proteins (WSCPs) stand out for their tunable optical properties and biocompatibility. Among them, the Class I WSCP from Chenopodium album (CaWSCP) exhibits unique photoconversion-induced red-shifts in absorption, enabling enhanced PA imaging through complete background subtraction and improved deep tissue imaging. To further expand its functionality, CaWSCP was engineered with a SpyTag-SpyCatcher system, enabling site-specific conjugation with HER2-specific affibodies for precise molecular targeting. Experimental findings demonstrate CaWSCP's biocompatibility, photoconversion capabilities, and potential for targeted imaging, making it a promising platform for advanced biomedical applications.Clinical Relevance- The engineered CaWSCP contrast agent, with its targeting capability via the SpyTag-SpyCatcher system, improves PA imaging for non-invasive detection and monitoring of cancer and vascular disorders by enhancing resolution and minimizing background interference.