Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd 3+ complexes at very high loadings (15.5–28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r 1 relaxivities of these nanoparticles range from 4.1 to 8.4 mM ？1s ？1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro.
References
[1]
Bradley, W.G., Jr.; Stark, D. Magnetic Resonance Imaging; Mosby: St. Louis, MO, USA, 1999.
[2]
Merbach, A.E.; Helm, L.; Toth, E. The Chemistry of Contrast Agents in Medical Magnetic Resonance Imaging; John Wiley and Sons: Chichester, UK, 2001.
[3]
Lauffer, R.B.; McMurry, T.J.; Ellison, J.J.; Caravan, P. Gadolinium(III) chelates as MRI contrast agents: Structure, dynamics, and applications. Chem. Rev. 1999, 99, 2293–2352. 11749483
[4]
Hyeon, T.; Piao, Y.; Kim, J. Multifunctional nanostructured materials for multimodal imaging, and simultaneous imaging and therapy. Chem. Soc. Rev. 2009, 28, 372–390.
[5]
Meade, T.J.; Miqin, M.Z.; Lanza, G.; Hyeon, T.; Lin, W. Magnetic nanoparticles for early detection of cancer by magnetic resonance imaging. MRS Bull. 2009, 34, 441–448, doi:10.1557/mrs2009.120.
[6]
Basilion, J.P.; Chiocca, E.A.; Benveniste, H.; Bhorade, R.; Mahmood, U.; Moore, A.; Weissleder, R. In vivo magnetic resonance imaging of transgene expression. Nat. Med. 2000, 6, 351–354, doi:10.1038/73219. 10700241
[7]
Wickline, S.A.; Lanza, G.M.; Morawski, A.M. Targeted contrast agents for magnetic resonance imaging and ultrasound. Curr. Opin. Biotechnol. 2005, 16, 89–92, doi:10.1016/j.copbio.2004.11.001. 15722020
[8]
Fisher, E.A.; Fayad, Z.A.; Williams, K.J.; Ma, Y.; Frias, J.C. Properties of a versatile nanoparticle platform contrast agent to image and characterize atherosclerotic plaques by magnetic resonance imaging. Nano Lett. 2006, 6, 2220–2224, doi:10.1021/nl061498r. 17034087
[9]
Lin, W.; Lin, W.; An, H.; Taylor, K.M.L.; Rieter, W.J. Nanoscale metal organic frameworks as potential multimodal contrast agents. J. Am. Chem. Soc. 2006, 128, 9024–9025, doi:10.1021/ja0627444. 16834362
Cui, F.-Z.; Chen, X.-H.; Fan, Y.-W.; Pang, W.-Q.; Luo, Z.-S.; Cai, Q. Dilute solution routes to various controllable morphologies of MCM-41 silica with a basic medium. Chem. Mater. 2001, 13, 258–263, doi:10.1021/cm990661z.
[23]
Tsutsumi, K.; Matsumoto, A.; Unger, K.K.; Grun, M. Novel pathways for the preparation of mesoporous MCM-41 materials: Control of porosity and morphology. Microporous Mesoporous Mater. 1999, 27, 207–216, doi:10.1016/S1387-1811(98)00255-8.
[24]
Mou, C.-Y.; Hung, Y.; Wu, S.-H.; Lu, F. Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles. Small 2009, 5, 1408–1413, doi:10.1002/smll.200900005. 19296554
[25]
Kuroda, K.; Yamauchi, Y.; Tonegawa, A.; Aoyama, Y.; Urata, C. Dialysis process for the removal of surfactants to form colloidal mesoporous silica nanoparticles. Chem. Commun. 2009, 5094–5096.
[26]
Haynes, C.L.; Abadeer, N.; Lin, Y.-S. Stability of small mesoporous silica nanoparticles in biological media. Chem. Commun. 2010, 47, 532–534.
[27]
Yin, Y.; Zhang, T.; Zhang, Q.; Ge, J. Core-satellite nanocomposite catalysts protected by a porous silica shell: Controllable reactivity, high stability, and magnetic recyclability. Angew. Chem. Int. Ed. 2008, 47, 8924–8928, doi:10.1002/anie.200803968.
[28]
Lin, V.S.-Y.; Pruski, M.; Wiench, J.W.; Huh, S.; Chen, H.-T. Dialkylaminopyridine-functionalized mesoporous silica nanosphere as an efficent and highly stable heterogeneous nucleophillic catalyst. J. Am. Chem. Soc. 2005, 127, 13305–13311, doi:10.1021/ja0524898. 16173762
Xia, Y.; Sun, Y.; Campbell, C.T.; Fanson, P.T.; Grayson, B.; Cho, E.C.; Li, W.; Cobley, C.M.; Yang, Y.; Lim, B.; Dai, Y. A sinter resistant catalytic system based on platinum nanoparticles supported on TiO2 nanofibers and covered by porous silica. Angew. Chem. Int. Ed. 2010, 49, 8165–8168, doi:10.1002/anie.201001839.
[31]
Zink, J.I.; Tamanoi, F.; Nel, A.E.; Ruehm, S.G.; Xia, T.; Kovochich, M.; Liu, J.; Liong, M. Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2008, 2, 889–896, doi:10.1021/nn800072t. 19206485
[32]
Stoddart, J.F.; Zink, J.I.; Zhao, Y.L.; Thomas, C.R.; Ambrogio, M.W. Mechanized silica nanoparticles: A new frontier in theranostic nanomedicine. Acc. Chem. Res. 2011, 44, 903–913, doi:10.1021/ar200018x. 21675720
[33]
Carter, M.B.; Phillips, B.; Liu, J.; Hanna, T.N.; Brown, P.A.; Durfee, P.N.; Padilla, D.; Phillips, G.K.; Carnes, E.C.; Ashley, C.E.; et al. The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers. Nat. Mater. 2011, 10, 389–397, doi:10.1038/nmat2992. 21499315
[34]
Brinker, C.J.; Jiang, X.; Stace-Naughton, A.; Liu, J. Porous nanoparticle supported lipid bilayers (protocells) as delivery vehicles. J. Am. Chem. Soc. 2009, 131, 1354–1355, doi:10.1021/ja808018y. 19173660
[35]
Lin, V.S.-Y.; Trewyn, B.G.; Slowing, I. Effect of surface functionalization of MCM-41-type mesoporous silica nanoparticles on the endocytosis by human cancer cells. J. Am. Chem. Soc. 2006, 128, 14792–14793, doi:10.1021/ja0645943. 17105274
[36]
Lin, V.S.-Y.; Trewyn, B.G.; Slowing, I. Mesoporous silica nanoparticles for intracellular delivery of membrane-impermeable proteins. J. Am. Chem. Soc. 2007, 129, 8845–8849, doi:10.1021/ja0719780. 17589996
[37]
Feng, P.; Liu, J.; Liao, P.; Liu, R. Responsive polymer-coated mesoporous silica as a pH-sensitive nanocarrier for controlled release. Langmuir 2011, 27, 3095–3099, doi:10.1021/la104973j.
[38]
Feng, P.; Zhang, Y.; Liu, R. Multiresponsive supramolecular nanogated ensembles. J. Am. Chem. Soc. 2009, 131, 15128–15129, doi:10.1021/ja905288m. 19746981
Lin, W.; Lin, W.; An, H.; Rieter, W.J.; Kim, J.S.; Taylor, K.M.L. Mesoporous silica nanospheres as highly efficent MRI contrast agents. J. Am. Chem. Soc. 2008, 130, 2154–2155, doi:10.1021/ja710193c. 18217764
[41]
Lin, V.S.-Y.; Pruski, M.; Song, S.; Trewyn, B.G.; Wiench, J.W.; Huh, S. Tuning of particle morphology and pore properties in mesoporous silicas with multiple functional groups. Chem. Commun. 2003, 2364–2365.
[42]
Lin, V.S.-Y.; Pruski, M.; Yoo, J.-C.; Wiench, J.W.; Huh, S. Organic functionalization and morphology control of mesoporous silicas via a Co-condensation synthesis method. Chem. Mater. 2003, 15, 4247–4256, doi:10.1021/cm0210041.
[43]
Kok, R.J.; Molema, G.; Schiffelers, R.M.; Temming, K. RGD-based strategies for selective delivery of therapuetics and imaging agents to the tumour vasculature. Drug Resist. Updat. 2005, 8, 381–402, doi:10.1016/j.drup.2005.10.002. 16309948
