Theranostic Anticancer Agents Based on Internally Functionalized ORMOSIL Nanoparticles
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Theranostic Anticancer Agents Based on Internally Functionalized ORMOSIL Nanoparticles Nathan I. Walton, Zhe Gao and Ilya Zharov Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA ABSTRACT We prepared organically modified silica (ORMOSIL) nanoparticles with internal functional groups and mesoporosity, suitable for the incorporation of modalities for both MRI imaging and cancer treatment by neutron capture therapy using gadolinium-157 nuclei. These modalities were incorporated by preparing ORMOSIL nanoparticles with reactive functional groups throughout the nanoparticle body, followed by their conversion into the metal chelating moieties inside the nanoparticles. INTRODUCTION Nanoparticles that can bind metals have potential applications in medical treatment for diseases that involve the buildup of metals in the body, such as Alzheimer's and Parkinson's disease, [1] in metal sequestering for water treatment, [2] fluorescence enhancement, [3] and as carriers for MRI contrast agents. [3-5] Most of these metal binding nanoparticles utilize thiol or polyamino carboxylic acid groups to chelate metals. [2,3-7] Silica nanoparticles, because of their uniform sizes, inert nature and low toxicity may act as useful supports for metal chelator functionalities. Recently, several metal chelating nanoparticles have been synthesized using thiol- or amino-containing silanes. [7,8] In the case of amino-containing silanes, a second step is required to convert them to polyamino carboxylic acid functionalities. The number of organic functionalities on the silica nanoparticle surface is dependent on the available silanols. Potentially, larger amounts of metals can be chelated if the number of the silica nanoparticle's available organic groups are increased. This can be accomplished by increasing the surface area of the silica nanoparticle. Silica particle surface area can be increased by creating mesopores (2-30 nm in diameter) in the silica nanoparticle. [9] This results in mesoporous silica nanoparticles (MSNs) that have a larger surface area while maintaining the same particle volume, compared to non-porous silica particles of identical size. MSNs can thus provide more silanols available for organosilane modification. There are two main methodologies in attaching an organosilane to the surface of MSNs. The post-modification with organosilanes provides well-defined structures but can give a nonuniform distribution of the surface functional groups and potentially block the pores. [10] The second method involves the co-condensation of an organosilane (e.g. 3-aminopropyltriethoxysilane, APTES) and a tetraalkoxysilane, e.g. tetraethyl orthosilicate (TEOS). This "one-pot" synthesis provides a uniform distribution of the functional groups with no pore blocking. However, there is a limit to the degree of functionalization because increasing the concentration of the organosilane perturbs the mesoporous structure. [11] Recently, it has been demonstrated that nanoparticles with large gadolinium loading have greater r1 and
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