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

通过逆电子需求狄尔斯-阿尔德点击化学实现脂质体纳米粒子的特异性结合

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作者:Christian Brand, Pasquale Iacono, Carlos Pérez-Medina, Willem J M Mulder, Moritz F Kircher, Thomas Reiner

Abstract

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.

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