Browsing by Author "Ananta, Jeyarama S."

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    Encapsulation of α-Particle–Emitting225Ac3+ Ions Within Carbon Nanotubes
    (Society of Nuclear Medicine and Molecular Imaging, 2015) Matson, Michael L.; Villa, Carlos H.; Ananta, Jeyarama S.; Law, Justin J.; Scheinberg, David A.; Wilson, Lon J.; Smalley Institute for Nanoscale Science and Technology
    225Ac3+ is a generator of α-particle–emitting radionuclides with 4 net α-particle decays that can be used therapeutically. Targeting 225Ac3+ by use of ligands conjugated to traditional bifunctional chelates limits the amount of 225Ac3+ that can be delivered. Ultrashort, single-walled carbon nanotubes (US-tubes), previously demonstrated as sequestering agents of trivalent lanthanide ions and small molecules, also successfully incorporate 225Ac3+. Methods: Aqueous loading of both 225Ac3+ ions and Gd3+ ions via bath sonication was used to construct 225Ac@gadonanotubes (225Ac@GNTs). The 225Ac@GNTs were subsequently challenged with heat, time, and human serum. Results: US-tubes internally loaded with both 225Ac3+ ions and Gd3+ ions show 2 distinct populations of 225Ac3+ ions: one rapidly lost in human serum and one that remains bound to the US-tubes despite additional challenge with heat, time, and serum. The presence of the latter population depended on cosequestration of Gd3+ and 225Ac3+ ions. Conclusion: US-tubes successfully sequester 225Ac3+ ions in the presence of Gd3+ ions and retain them after a human serum challenge, rendering 225Ac@GNTs candidates for radioimmunotherapy for delivery of 225Ac3+ ions at higher concentrations than is currently possible for traditional ligand carriers.
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    Enhanced MRI relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs
    (Wiley, 2012) Sethi, Richa; Ananta, Jeyarama S.; Karmonik, Christof; Zhong, Meng; Fung, Steve H.; Liu, Xuewu; Li, King; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo; Smalley Institute for Nanoscale Science and Technology; Center for Biological and Environmental Nanotechnology
    Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2− (Magnevist®) into the pores of injectable mesoporous silicon particles. Nanoconstructs with three different pore sizes were studied, and at 60 MHz, they exhibited longitudinal relaxivities of ~24 m m−1 s−1 for 5–10 nm pores and ~10 m m−1 s−1 for 30 – 40 nm pores. No enhancement in relaxivity was observed for larger pores sizes. Using an outer-sphere compound, [GdTTHA]3−, and mathematical modeling, it was demonstrated that the relaxivity enhancement is due to the increase in rotational correlation times (CA adsorbed on the pore walls) and diffusion correlation times (reduced mobility of the water molecules), as the pore sizes decreases. It was also observed that extensive CA adsorption on the outer surface of the silicon particles negates the advantages offered by nanoscale confinement. Upon incubation with HeLa cells, the nanoconstructs did not demonstrate significant cytotoxicity for up to 3 days post incubation, at different particle/cell ratios. In addition, the nanoconstructs showed complete degradation after 24 h of continuous agitation in phosphate-buffered saline. These data support and confirm the hypothesis that the geometrical confinement of Gd3+-chelate compounds into porous structures offers MRI nanoconstructs with enhanced relaxivity (up to 6 times for [Gd(DTPA)(H2O)]2−, and 4 times for [GdTTHA]3−) and, potentially, improved stability, reduced toxicity and tissue specificity.