We
present a robust and general method for embedding nano
particles, such as quantum dots (QD) or colloidalgold (Au) nanocrystals, into a highly water-soluble thin silica shell do
ped with
paramagnetic gadolinium(Gd
3+) ions without negatively im
pacting the o
ptical
pro
perties of the QD or Au nano
particle cores. Theultrathin silica shell has been covalently linked to Gd
3+ ions chelator, tetraazacyclododecanetetraacetic acid(DOTA). The resulting com
plex has a diameter of 8 to 15 nm and is soluble in high ionic strength buffers at
pH values ranging from a
pproximately 4 to 11. For this system, nano
particle concentrations exceed 50
![](/images/entities/mgr.gif)
M,while most other nano
particles might aggregate. In magnetic resonance imaging (MRI) ex
periments atclinical magnetic field strengths of 1.4 T (
1H resonance frequency of 60 MHz), the gadolinium-DOTA (Gd-DOTA) attached to SiO
2-coated QDs has a s
pin-lattice (
T1)
particle relaxivity (
r1) and a s
pin-s
pin (
T2)
particle relaxivity (
r2) of 1019 ± 19 mM
-1s
-1 and 2438 ± 46 mM
-1 s
-1, res
pectively, for a 8-nm QD. The
particle relaxivity has been correlated to the number of Gd
3+ covalently linked to the silica shell. At 1.4 T,the Gd-DOTA ion relaxivities,
r1 and
r2, res
pectively, 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
particlesa
pproximately 15 nm in diameter. Preliminary dynamic contrast enhancement MRI ex
periments 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 a
pproach may offer numerous advantages over other similara
pproaches,
1,2p074072pb00002"> 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.