Paramagnetic Silica-Coated Nanocrystals as an Advanced MRI Contrast Agent

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• 作者：Daniele Gerion ; Julie Herberg ; Robert Bok ; Erica Gjersing ; Erick Ramon ; Robert Maxwell ; John Kurhanewicz ; Thomas F. Budinger ; Joe W. Gray ; Marc A. Shuman ; Fanqing Frank Chen
• 刊名：Journal of Physical Chemistry C
• 出版年：2007
• 出版时间：August 30, 2007
• 年：2007
• 卷：111
• 期：34
• 页码：12542 - 12551
• 全文大小：312K
• 年卷期：v.111,no.34(August 30, 2007)
• ISSN：1932-7455

文摘

We present a robust and general method for embedding nanoparticles, such as quantum dots (QD) or colloidalgold (Au) nanocrystals, into a highly water-soluble thin silica shell doped with paramagnetic gadolinium(Gd³⁺) ions without negatively impacting the optical properties of the QD or Au nanoparticle cores. Theultrathin silica shell has been covalently linked to Gd³⁺ ions chelator, tetraazacyclododecanetetraacetic acid(DOTA). The resulting complex has a diameter of 8 to 15 nm and is soluble in high ionic strength buffers atpH values ranging from approximately 4 to 11. For this system, nanoparticle concentrations exceed 50 M,while most other nanoparticles might aggregate. In magnetic resonance imaging (MRI) experiments atclinical magnetic field strengths of 1.4 T (¹H resonance frequency of 60 MHz), the gadolinium-DOTA (Gd-DOTA) attached to SiO₂-coated QDs has a spin-lattice (T₁) particle relaxivity (r₁) and a spin-spin (T₂)particle relaxivity (r₂) of 1019 ± 19 mM^-1s^-1 and 2438 ± 46 mM^-1 s^-1, respectively, for a 8-nm QD. Theparticle relaxivity has been correlated to the number of Gd³⁺ covalently linked to the silica shell. At 1.4 T,the Gd-DOTA ion relaxivities, r₁ and r₂, respectively, are 23 ± 0.40 mM^-1s^-1 and 54 ± 1.0 mM^-1s^-1. Thesensitivity of our probes is in the 100-nM range for 8-10 nm particles and reaches 10 nM for particlesapproximately 15 nm in diameter. Preliminary dynamic contrast enhancement MRI experiments in mice revealedthat silica-coated MRI probes are cleared from the renal system into the bladder with no observable affectson the health of the animal. This current approach may offer numerous advantages over other similarapproaches,^1,2 including greater relaxivity and greater simplicity for the synthesis process of dual modalitycontrast agents that allow both MRI and optical detection as well as applicability to other nanoparticles.