Paramagnetic silica-coated nanocrystals as an advanced MRI contrast agent

被引:63
作者
Gerion, Daniele
Herberg, Julie
Bok, Robert
Gjersing, Erica
Ramon, Erick
Maxwell, Robert
Kurhanewicz, John
Budinger, Thomas F.
Gray, Joe W.
Shuman, Marc A.
Chen, Fanqing Frank
机构
[1] Lawrence Livermore Natl Lab, Livermore, CA 94588 USA
[2] Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA
[3] Lawrence Livermore Natl Lab, Livermore, CA 94551 USA
[4] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94115 USA
关键词
D O I
10.1021/jp074072p
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
We present a robust and general method for embedding nanoparticles, such as quantum dots (QD) or colloidal gold (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. The ultrathin 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 at pH values ranging from approximately 4 to 11. For this system, nanoparticle concentrations exceed 50 AM, while most other nanoparticles might aggregate. In magnetic resonance imaging (MRI) experiments at clinical magnetic field strengths of 1.4 T (H-1 resonance frequency of 60 MHz), the gadolinium- DOTA (Gd-DOTA) attached to SiO2-coated QDs has a spin-lattice (T-1) particle relaxivity (r(1)) and a spin-spin (T-2) particle relaxivity (r(2)) of 1019 +/- 19 mM(-1)s(-1) and 2438 +/- 46 mM(-1) s(-1), respectively, for a 8-nm QD. The particle relaxivity has been correlated to the number of Gd3+ covalently linked to the silica shell. At 1.4 T, the Gd-DOTA ion relaxivities, r(1) and r(2), respectively, are 23 +/- 0.40 mM(-1)s(-1) and 54 +/- 1.0 mM(-1)s(-1). The sensitivity of our probes is in the 100-nM range for 8-10 nm particles and reaches 10 nM for particles approximately 15 nm in diameter. Preliminary dynamic contrast enhancement MRI experiments in mice revealed that silica-coated MRI probes are cleared from the renal system into the bladder with no observable affects on the health of the animal. This current approach may offer numerous advantages over other similar approaches, (1,2) including greater relaxivity and greater simplicity for the synthesis process of dual modality contrast agents that allow both MRI and optical detection as well as applicability to other nanoparticles.
引用
收藏
页码:12542 / 12551
页数:10
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