Abstract
A novel photo-click-based platform has been developed for rapid screening and affinity optimization of heterobivalent agents. This method allows for the efficient selection of high-affinity dual receptor-targeting agents via streamlining tedious organic synthesis and biological evaluation procedures required by traditional approaches. The high-avidity heterobivalent agents targeting both integrin αvβ3 and urokinase-type plasminogen activator receptors have been developed using this photo-click-facilitated screening platform. The affinity screening results were further validated by traditional in vitro and in vivo evaluation techniques, reaffirming the reliability of the method. The convenience, rapidity, universality, and robustness of the screening platform, discussed in this report, can greatly facilitate the development of new heterobivalent agents for research and/or clinical applications.