Specific Binding of Liposomal Nanoparticles through Inverse Electron‐Demand Diels–Alder Click Chemistry

Here, we report a method to specifically bind liposomal radiopharmaceuticals to a CoCrMo alloy, which can be used in arterial stents, via an irreversible inverse electron‐demand Diels–Alder reaction. Inspired by recent accomplishments in pre‐targeted imaging using tetrazine‐trans‐cyclooctene click chemistry, we synthesized (89)Zr‐labeled trans‐cyclooctene‐functionalized liposomal nanoparticles, which were validated on a tetrazine‐appended polydopamine‐coated CoCrMo surface. In efforts to ultimately translate this new material to biomedical applications, we compared the ability of (89)Zr‐TCO–liposomal nanoparticles ((89)Zr‐TCO‐LNP) to be immobilized on the tetrazine surface to the control suspensions of non‐TCO functionalized (89)Zr‐liposomal nanoparticles. Ultimately, this platform technology could result in a systemic decrease of the radiotherapeutic dose deposited in non‐targeted tissues by specific removal of long‐circulating liposomal radiopharmaceuticals from the blood pool.