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 ⁸⁹Zr-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 ⁸⁹Zr-TCO-liposomal nanoparticles (⁸⁹Zr-TCO-LNP) to be immobilized on the tetrazine surface to the control suspensions of non-TCO functionalized ⁸⁹Zr-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.