Browsing by Author "Gizzatov, Ayrat"

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    Carbon and Silicon Nanomaterials for Medical Nanotechnology Applications
    (2015-05-18) Gizzatov, Ayrat; Wilson, Lon J.; Tour, James M; Vajtai, Robert; Decuzzi, Paolo
    This dissertation focuses on the development of sp2-carbon- and silicon-based nanomaterials for medical diagnostics and in vivo magnetic field-guided delivery applications. To realize these applications, especially for the development of new in vivo Magnetic Resonance Imaging (MRI) contrast agents (CAs), high solubility in aqueous media is required. Therefore, this work first details development of a new non-covalent method for the preparation of stable aqueous colloidal solution of surfactant-free sp2-carbon nanostructures, as well as a second rapid covalent functionalization procedure to produce highly-water-dispersible honey-comb carbon nanostructures (ca. 50 mg/mL). Next, highly-water-dispersible graphene nanoribbons and Gd3+ ions were together used to produce a high-performance MRI CA for T1- and T2- weighted imaging. In terms of its relaxivity (r1,2) values, this new CA material outperforms currently-available clinical CAs by up to 16 times for r1 and 21 times for r2. Finally, sub-micrometer discoidal magnetic nanoconstructs have been produced and studied for applications for in vivo magnetic-field-guided delivery into cancerous tumors. The nanoconstructs were produced by confining ultra-small superparamagnetic iron oxide nanoparticles (USPIOs) within mesoporous silicon which produced T2-weighted MRI CA performance 2.5 times greater than for the free USPIOs themselves. Moreover, these nanoconstructs, under the influence of an external magnetic field, collectively cooperated via a new mechanism to amplify accumulation in melanoma tumors of mice. Overall, the results of this dissertation could aid in the rapid translation of these nanotechnologies into the clinic, while, hopefully, also serving as an inspiration for continued research into the field of Medical Nanotechnology.
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    Enhanced MRI relaxivity of aquated Gd3+ﾠions by carboxyphenylated water-dispersed graphene nanoribbons
    (Royal Society of Chemistry, 2014) Gizzatov, Ayrat; Keshishian, Vazrik; Guven, Adem; Dimiev, Ayrat M.; Qu, Feifei; Muthupillai, Raja; Decuzzi, Paolo; Bryant, Robert G.; Tour, James M.; Wilson, Lon J.; Richard E. Smalley Institute for Nanoscale Science and Technology
    The present study demonstrates that highly water-dispersed graphene nanoribbons dispersed by carboxyphenylated substituents and conjugated to aquated Gd3+ﾠions can serve as a high-performance contrast agent (CA) for applications inﾠT1- andﾠT2-weighted magnetic resonance imaging (MRI) with relaxivity (r1,2) values outperforming currently-available clinical CAs by up to 16 times forﾠr1ﾠand 21 times forﾠr2.
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    Geometrical confinement of Gd(DOTA) molecules within mesoporous silicon nanoconstructs for MR imaging of cancer
    (Elsevier, 2014) Gizzatov, Ayrat; Stigliano, Cinzia; Ananta, Jeyerama S.; Sethi, Richa; Xu, Rong; Guven, Adem; Ramirez, Maricela; Shen, Haifa; Sood, Anil; Ferrari, Mauro; Wilson, Lon J.; Liu, Xuewu; Decuzzi, Paolo; Smalley Institute for Nanoscale Science and Technology
    Porous silicon has been used for the delivery of therapeutic and imaging agents in several biomedical applications. Here, mesoporous silicon nanoconstructs (SiMPs) with a discoidal shape and a sub-micrometer size (1,000 × 400 nm) have been conjugated with gadolinium-tetraazacyclododecane tetraacetic acid Gd(DOTA) molecules and proposed as contrast agents for Magnetic Resonance Imaging. The surface of the SiMPs with different porosities – small pore (SP: ~ 5 nm) and huge pore (HP: ~ 40 nm) – and of bulk, non-porous silica beads (1,000 nm in diameter) have been modified with covalently attached (3-aminopropyl)triethoxysilane (APTES) groups, conjugated with DOTA molecules, and reacted with an aqueous solution of GdCl3. The resulting Gd(DOTA) molecules confined within the small pores of the Gd-SiMPs achieve longitudinal relaxivities r1 of ~ 17 (mM·s)−1, which is 4 times greater than for free Gd(DOTA). This enhancement is ascribed to the confinement and stable chelation of Gd(DOTA) molecules within the SiMP mesoporous matrix. The resulting nanoconstructs possess no cytotoxicity and accumulate in ovarian tumors up to 2% of the injected dose per gram tissue, upon tail vein injection. All together this data suggests that Gd-SiMPs could be efficiently used for MR vascular imaging in cancer and other diseases.
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    Hierarchically Structured Magnetic Nanoconstructs with Enhanced Relaxivity and Cooperative Tumor Accumulation
    (Wiley, 2014) Gizzatov, Ayrat; Key, Jaehong; Aryal, Santosh; Ananta, Jeyarama; Cervadoro, Antonio; Palange, Anna Lisa; Fasano, Matteo; Stigliano, Cinzia; Zhong, Meng; Di Mascolo, Daniele; Guven, Adem; Chiavazzo, Eliodoro; Asinari, Pietro; Liu, Xuewu; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo; R.E. Smalley Institute for Nanoscale Science and Technology
    Iron oxide nanoparticles are formidable multifunctional systems capable of contrast enhancement in magnetic resonance imaging, guidance under remote fields, heat generation, and biodegradation. Yet, this potential is underutilized in that each function manifests at different nanoparticle sizes. Here, sub-micrometer discoidal magnetic nanoconstructs are realized by confining 5 nm ultra-small super-paramagnetic iron oxide nanoparticles (USPIOs) within two different mesoporous structures, made out of silicon and polymers. These nanoconstructs exhibit transversal relaxivities up to ≈10 times (r 2 ≈ 835 mm −1 s−1) higher than conventional USPIOs and, under external magnetic fields, collectively cooperate to amplify tumor accumulation. The boost in r 2 relaxivity arises from the formation of mesoscopic USPIO clusters within the porous matrix, inducing a local reduction in water molecule mobility as demonstrated via molecular dynamics simulations. The cooperative accumulation under static magnetic field derives from the large amount of iron that can be loaded per nanoconstuct (up to ≈65 fg) and the consequential generation of significant inter-particle magnetic dipole interactions. In tumor bearing mice, the silicon-based nanoconstructs provide MRI contrast enhancement at much smaller doses of iron (≈0.5 mg of Fe kg−1 animal) as compared to current practice.
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    Surfactant-free Gd3+-ion-containing carbon nanotube MRI contrast agents for stem cell labeling
    (Royal Society of Chemistry, 2015) Gizzatov, Ayrat; Hernández-Rivera, Mayra; Keshishian, Vazrik; Mackeyev, Yuri; Law, Justin J.; Guven, Adem; Sethi, Richa; Qu, Feifei; Muthupillai, Raja; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Ma, Qing; Bryant, Robert G.; Wilson, Lon J.; Richard E. Smalley Institute for Nanoscale Science and Technology
    There is an ever increasing interest in developing new stem cell therapies. However, imaging and tracking stem cells in vivo after transplantation remains a serious challenge. In this work, we report new, functionalized and high-performance Gd3+-ion-containing ultra-short carbon nanotube (US-tube) MRI contrast agent (CA) materials which are highly-water-dispersible (ca. 35 mg ml−1) without the need of a surfactant. The new materials have extremely high T1-weighted relaxivities of 90 (mM s)−1 per Gd3+ ion at 1.5 T at room temperature and have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for MR imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and TEM images of the labeled cells, in general, reveal small clusters of the CA material located within the cytoplasm with 109 Gd3+ ions per cell.