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Gadolinium-incorporated mesoporous silica nanoparticles.


Shan L.


Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.
2011 Jul 11 [updated 2011 Aug 10].


The gadolinium (Gd3+)-incorporated mesoporous silica nanoparticle (NP), abbreviated as Gd2O3@SiO2, is a non-targeted contrast agent developed by Shao et al. for magnetic resonance imaging (MRI) of tumors (1). The application of NPs in molecular imaging and drug delivery is currently undergoing a tremendous expansion because of the unique features of NPs, including high stability, high carrier capacity, incorporation feasibility of both hydrophilic and hydrophobic substances, controlled release of drug payloads, and biocompatibility (2-5). The design of NP-based paramagnetic contrast agents must meet certain criteria, which are different from the criteria for the development and use of NPs in drug delivery. For example, paramagnetic metals incorporated into the NPs should be easily accessed by a large number of labile water molecules (6, 7). NP agents must also be stable and safe when used in clinic, and must exhibit isotropic and slow tumbling motion when used in vivo. Silica inorganic NPs are well qualified for use in contrast agent development because they have a mesoporous structure, their sizes can be tuned from 1.5 nm to 30 nm, and they offer large surface areas (>1,000 m2/g) for ligand conjugation (5, 6). Functionalization of the internal surface of silica NPs via the use of alkoxysilanes allows the surface properties to be tailored for various purposes. In general, Gd3+-labeled silica NPs are designed either by incorporating Gd3+ into silica or by grafting Gd3+-chelates onto the NP surface (6, 7). Incorporating Gd3+ into silica results in contrast agents with a high relaxivity because of the high payload of Gd3+ and the slow tumbling motion of the NPs. Grafting Gd3+-chelates onto the NP surface may limit the Gd3+ loading because of the reduced number of available anchoring sites on the NP surface. MRI studies have confirmed the usefulness of silica NP-based contrast agents in animal models of human disease. However, numerous questions remain to be addressed for their application in humans. Because the synthetic methods and the nanomaterials for synthesis are highly versatile, it is difficult to determine the relationship between the chemical physical properties of NPs and their in vivo behaviors. The ultimate fate and toxicity of NPs themselves and their metabolites are still poorly understood (7, 8). As discussed in detail by Fadeel and Garcia-Bennett, silica NPs are commonly prepared by the sol-gel process, which generates silica NPs through the hydrolysis and polycondensation of silicon alkoxide (7). The sol-gel technique is also popular for the synthesis of other types of NPs because the NP properties, such as particle size, pore size, amount of incorporated metals, and surface functional groups, can be easily controlled (4, 7). Synthesis of NPs with the sol-gel technique is also cost-effective on the laboratory scale. Shao et al. reported a one-step synthesis of Gd3+-incorporated silica NPs (Gd2O3@SiO2) with a mesoporous structure and high surface area (1). The NPs possess desirable MRI contrast enhancement properties, making them suitable for potential application as target-specific contrast agents for molecular MRI. This chapter summarizes data regarding Gd2O3@SiO2 (1).

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