Gadolinium Nanoparticles Conjugated with Therapeutic Bifunctional Chelate as a Potential <I>T</I><SUB>1</SUB> Theranostic Magnetic Resonance Imaging Agent

This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponding low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B.