Lee, Dong-Eun Na, Jin Hee Lee, Sanzmin Kang, Choong Mo Kim, Hun Nyun Han, Seung Jin Kim, Hyunjoon Choe, Yearn Seong Jung, Kyung-Ho Lee, Kyo Chul Choi, Kuiwon Kwon, Ick Chan Jeong, Seo Young Lee, Kyung-Han Kim, Kwangmeyung 2024-01-20T12:04:45Z 2024-01-20T12:04:45Z 2021-09-05 2013-06 1543-8384 https://pubs.kist.re.kr/handle/201004/128008 An efficient and straightforward method for radiolabeling nanoparticles is urgently needed to understand the in vivo biodistribution of nanoparticles. Herein, we investigated a facile and highly efficient strategy to prepare radiolabeled glycol chitosan nanoparticles with Cu-64 via a strain promoted azide-alkyne cycloaddition strategy, which is often referred to as click chemistry. First, the azide (N-3) group, which allows for the preparation of radiolabeled nanoparticles by copper-free click chemistry, was incorporated to glycol chitosan nanoparticles (CNPs). Second, the strained cyclooctyne derivative, dibenzyl cyclooctyne (DBCO) conjugated with a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelator, was synthesized for preparing the preradiolabeled alkyne complex with Cu-64 radionuclide. Following incubation with the Cu-64-radiolabeled DBCO complex (DBCO-PEG(4)-Lys-DOTA-Cu-64 with high specific activity, 18.5 GBq/mu mol), the azide-functionalized CNPs were radiolabeled successfully with Cu-64, with a high radiolabeling efficiency and a high radiolabeling yield (>98%). Importantly, the radiolabeling of CNPs by copper free click chemistry was accomplished within 30 mm, with great efficiency in aqueous conditions In addition, we found that the Cu-64-radiolabeled CNPs (Cu-64-CNPs) did not show any significant effect on the physicochemical properties, such as size, zeta potential, or spherical morphology. After Cu-64-CNPs were intravenously administered to tumor bearing mice, the real-time, in vivo biodistribution and tumor targeting ability of Cu-64-CNPs were quantitatively evaluated by microPET images of tumor bearing mice. These results demonstrate the benefit of copper free click chemistry as a facile, preradiolabeling approach to conveniently radiolabel nanoparticles for evaluating the real-time in vivo biodistribution of nanoparticles. English AMER CHEMICAL SOC IRON-OXIDE NANOPARTICLES IN-VIVO BIODISTRIBUTION QUANTUM DOTS MULTIFUNCTIONAL NANOPARTICLES DRUG DEVELOPMENT TUMOR CONJUGATION CLEARANCE MICE THERAGNOSIS Facile Method To Radiolabel Glycol Chitosan Nanoparticles with Cu-64 via Copper-Free Click Chemistry for MicroPET Imaging Article 10.1021/mp300601r 1 MOLECULAR PHARMACEUTICS, v.10, no.6, pp.2190 - 2198 MOLECULAR PHARMACEUTICS 10 6 2190 2198 scie scopus 000320015600010 2-s2.0-84878665586 Medicine, Research & Experimental Pharmacology & Pharmacy Research & Experimental Medicine Pharmacology & Pharmacy Article IRON-OXIDE NANOPARTICLES IN-VIVO BIODISTRIBUTION QUANTUM DOTS MULTIFUNCTIONAL NANOPARTICLES DRUG DEVELOPMENT TUMOR CONJUGATION CLEARANCE MICE THERAGNOSIS radiolabeling nanoparticles copper-free click chemistry microPET imaging