Browsing by Author "Wilson, Lon J."
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Item A New High-Performance Gadonanotube-Polymer Hybrid Material for Stem Cell Labeling and Tracking by MRI(Hindawi, 2018) Moghaddam, Sakineh E.; Hernández-Rivera, Mayra; Zaibaq, Nicholas G.; Ajala, Afis; Cabreira-Hansen, Maria da Graça; Mowlazadeh-Haghighi, Saghar; Willerson, James T.; Perin, Emerson C.; Muthupillai, Raja; Wilson, Lon J.A gentle, rapid method has been developed to introduce a polyacrylic acid (PAA) polymer coating on the surface of gadonanotubes (GNTs) which significantly increases their dispersibility in water without the need of a surfactant. As a result, the polymer, with its many carboxylic acid groups, coats the surface of the GNTs to form a new GNT-polymer hybrid material (PAA-GNT) which can be highly dispersed in water (ca. 20 mg·mL−1) at physiological pH. When dispersed in water, the new PAA-GNT material is a powerful MRI contrast agent with an extremely short water proton spin-lattice relaxation time (T1) which results in a T1-weighted relaxivity of 150 mM−1·s−1 per Gd3+ ion at 1.5 T. Furthermore, the PAA-GNTs have been used to safely label porcine bone-marrow-derived mesenchymal stem cells for magnetic resonance imaging. The labeled cells display excellent image contrast in phantom imaging experiments, and transmission electron microscopy images of the labeled cells reveal the presence of highly dispersed PAA-GNTs within the cytoplasm with 1014 Gd3+ ions per cell.Item A New Imaging Platform for Visualizing Biological Effects of Non-Invasive Radiofrequency Electric-Field Cancer Hyperthermia(Public Library of Science, 2015) Corr, Stuart J.; Shamsudeen, Sabeel; Vergara, Leoncio A.; Ho, Jason Chak-Shing; Ware, Matthew J.; Keshishian, Vazrik; Yokoi, Kenji; Savage, David J.; Meraz, Ismail M.; Kaluarachchi, Warna; Cisneros, Brandon T.; Raoof, Mustafa; Nguyen, Duy Trac; Zhang, Yingchun; Wilson, Lon J.; Summers, Huw; Rees, Paul; Curley, Steven A.; Serda, Rita E.Herein, we present a novel imaging platform to study the biological effects of non-invasive radiofrequency (RF) electric field cancer hyperthermia. This system allows for real-time in vivointravital microscopy (IVM) imaging of radiofrequency-induced biological alterations such as changes in vessel structure and drug perfusion. Our results indicate that the IVM system is able to handle exposure to high-power electric-fields without inducing significant hardware damage or imaging artifacts. Furthermore, short durations of low-power (< 200 W) radiofrequency exposure increased transport and perfusion of fluorescent tracers into the tumors at temperatures below 41°C. Vessel deformations and blood coagulation were seen for tumor temperatures around 44°C. These results highlight the use of our integrated IVM-RF imaging platform as a powerful new tool to visualize the dynamics and interplay between radiofrequency energy and biological tissues, organs, and tumors.Item An Assessment of Gadonanotubes as Magnetic Nanolabels for Improved Stem Cell Detection and Retention in Cardiomyoplasty(2013-07-24) Tran, Lesa; Wilson, Lon J.; Matsuda, Seiichi P. T.; Jacot, Jeffrey G.; Perin, Emerson C.; Cabreira, Maria da GraçaIn this work, gadolinium-based carbon nanocapsules are developed as a novel nanotechnology that addresses the shortcomings of current diagnostic and therapeutic methods of stem cell-based cardiomyoplasty. With cardiovascular disease (CVD) responsible for approximately 30% of deaths worldwide, the growing need for improved cardiomyoplasty has spurred efforts in nanomedicine to develop innovative techniques to enhance the therapeutic retention and diagnostic tracking of transplanted cells. Having previously been demonstrated as a high-performance T1-weighted magnetic resonance imaging (MRI) contrast agent, Gadonanotubes (GNTs) are shown for the first time to intracellularly label pig bone marrow-derived mesenchymal stem cells (MSCs). Without the use of a transfection agent, micromolar concentrations of GNTs deliver up to 10^9 Gd(III) ions per cell, allowing for MSCs to be visualized in a 1.5 T clinical MRI scanner. The cellular response to the intracellular incorporation of GNTs is also assessed, revealing that GNTs do not compromise the viability, differentiation potential, or phenotype characteristics of the MSCs. However, it is also found that GNT-labeled MSCs exhibit a decreased response to select cell adhesion proteins and experience a non-apoptotic, non-proliferative cell cycle arrest, from which the cells recover 48 h after GNT internalization. In tandem with developing GNTs as a new stem cell diagnostic agent, this current work also explores for the first time the therapeutic application of the magnetically-active GNTs as a magnetic facilitator to increase the retention of transplanted stem cells during cardiomyoplasty. In vitro flow chamber assays, ex vivo perfusion experiments, and in vivo porcine injection procedures all demonstrate the increased magnetic-assisted retention of GNT-labeled MSCs in the presence of an external magnetic field. These studies prove that GNTs are a powerful ‘theranostic’ agent that provides a novel platform to simultaneously monitor and improve the therapeutic nature of stem cells for the treatment of CVD. It is expected that this new nanotechnology will further catalyze the development of cellular cardiomyoplasty and other stem cell-based therapies for the prevention, detection, and treatment of human diseases.Item An electronic spectral study of some Fe(II) magnetic isomers in solution and a spectral-structural correlation with their Ni(II) analogs(1975) Georges, Danae; Wilson, Lon J.Pseudooctahedral Fe(II) Complexes of the hexadentate ligand, tris4-[(6-R)-2-pyridyl]-3-aza-3-butenylamine, where R is either H or CH^ (Figure 1) , have been studied in solution by electronic spectroscopy. The complexes represent a magnetically interesting series with Fe-I being low-spin, Fe-IV high-spin, and Fe-II and Fe-III spin equilibrium species. The d-d electronic spectrum of high-spin Fe-IV has been interpreted in terms of a strongly distorted octahedral ligand field model with 1 Dq = 11,4 cm. As evidenced by X-ray structural results, a major contribution of the reduction from symmetry appears to arise from a static molecular distortion in which the average Fe-N(imine) and Fe-N(pyridine) bond distances differ by .14. As for other low-spin tris(a-diimine)Fe(II) complexes, the spectrum of Fe-I is characterized by only Fe (II) -» l igand charge transfer bands whose intensities and positions obscure any d-d transitions. The spectrum of the spin equilibrium Fe-III compound displays features commensurate with a molefraction-weighted population of both high-spin and low-spin magnetic isomers with 1Dqhs (Fe-III) being ~11,7 cm-1 when the two spin states are nearly equi-energetic. The analogous Ni(II) complexes of Figure 1 have also been synthesized and characterized by elemental analysis, infrared spectroscopy, and solution conductivity, magnetic susceptibility, pmr, and d-d electronic spectral measurements. From the spectral studies, 1Dq values for the series are found to increase according to the sequence: Ni-IV (1,55 cm-1)Item Anthropogenic Carbon Nanotubes Found in the Airways of Parisian Children(Elsevier, 2015) Kolosnjaj-Tabi, Jelena; Just, Jocelyne; Hartman, Keith B.; Laoudi, Yacine; Boudjemaa, Sabah; Alloyeau, Damien; Szwarc, Henri; Wilson, Lon J.; Moussa, Fathi; Richard E. Smalley Institute for Nanoscale Science and TechnologyCompelling evidence shows that fine particulate matters (PMs) from air pollution penetrate lower airways and are associated with adverse health effects even within concentrations below those recommended by the WHO. A paper reported a dose-dependent link between carbon content in alveolar macrophages (assessed only by optical microscopy) and the decline in lung function. However, to the best of our knowledge, PM had never been accurately characterized inside human lung cells and the most responsible components of the particulate mix are still unknown. On another hand carbon nanotubes (CNTs) from natural and anthropogenic sources might be an important component of PM in both indoor and outdoor air. We used high-resolution transmission electron microscopy and energy dispersive X-ray spectroscopy to characterize PM present in broncho-alveolar lavage-fluids (n = 64) and inside lung cells (n = 5 patients) of asthmatic children. We show that inhaled PM mostly consist of CNTs. These CNTs are present in all examined samples and they are similar to those we found in dusts and vehicle exhausts collected in Paris, as well as to those previously characterized in ambient air in the USA, in spider webs in India, and in ice core. These results strongly suggest that humans are routinely exposed to CNTs.Item Biologically-compatible gadolinium(at)(carbon nanostructures) as advanced contrast agents for magnetic resonance imaging(2005) Sitharaman, Balaji; Wilson, Lon J.Paramagnetic gadolinium-based carbon nanostructures are introduced as a new paradigm in high-performance magnetic resonance imaging (MRI) contrast agent (CA) design. Two Gd C60-based nanomaterials, Gd C60 [C(COOH)2]10 and Gd C60(OH)x are shown to have MRI efficacies (relaxivities) 5 to 20 times larger than any current Gd3+-based CA in clinical use. The first detailed and systematic physicochemical characterization was performed on these materials using the same experimental techniques usually applied to traditional Gd 3+-based CAs. Water-proton relaxivities were measured for the first time on these materials, as a function of magnetic field (5 x 10-4--9.4 T) to elucidate the different interaction mechanisms and dynamic processes influencing the relaxation behavior. These studies attribute the observed enhanced relaxivities completely to the "outer sphere" proton relaxation mechanism. These "outer sphere" relaxation effects are the largest reported for any Gd3+-based agent without inner-sphere water molecules. The proton relaxivities displayed a remarkable pH-dependency, increasing dramatically with decreasing pH (pH: 3--12). The increase in relaxivity resulted mainly from aggregation and subsequent three-order-of-magnitude increase in tauR, the rotational correlation time. Water-soluble fullerene materials (such as the neuroprotective fullerene drug, C3) readily cross cell membranes, suggesting an application for these gadofullerenes as the first intracellular, as well as pH-responsive MRI CAs. Studies performed at 60 MHz in the presence of phosphate-buffered saline (PBS, mice serum pH: 7.4) to mimic physiological conditions demonstrated that the aggregates can be disrupted by addition of salts, leading to a decrease in relaxivity. Biological fluids present a high salt concentration and should strongly modify the behavior of any fullerenes/metallofullerene-based drug in vivo. Gd C60[C(COOH)2]10 also showed enhanced relaxivity (23% increase) in the presence of the blood protein, human serum albumin (HSA). This result suggests a strong non-covalent interaction between Gd C60[C(COOH)2]10 and HSA leading to slower rotation and a subsequent increase in relaxivity. This also suggests Gd C 60[C(COOH)2]10 as a promising candidate for non-invasive MR angiographic applications to image the "blood pool." Finally, the various important factors or parameters discussed in this work provide valuable insight that can, in general, be used not only for the development of other carbon nanostructure-based MRI contrast agents, but also for any fullerene-based biomedical application.Item Biotransport kinetics and intratumoral biodistribution of malonodiserinolamide-derivatized [60]fullerene in a murine model of breast adenocarcinoma(Dove Press, 2017) Lapin, Norman A.; Vergara, Leoncio A.; Mackeyev, Yuri; Newton, Jared M.; Dilliard, Sean A.; Wilson, Lon J.; Curley, Steven A.; Serda, Rita E.; The Smalley-Curl Institute for Nanoscale Science and Technology[60]Fullerene is a highly versatile nanoparticle (NP) platform for drug delivery to sites of pathology owing to its small size and both ease and versatility of chemical functionalization, facilitating multisite drug conjugation, drug targeting, and modulation of its physicochemical properties. The prominent and well-characterized role of the enhanced permeation and retention (EPR) effect in facilitating NP delivery to tumors motivated us to explore vascular transport kinetics of a water-soluble [60]fullerene derivatives using intravital microscopy in an immune competent murine model of breast adenocarcinoma. Herein, we present a novel local and global image analysis of vascular transport kinetics at the level of individual tumor blood vessels on the micron scale and across whole images, respectively. Similar to larger nanomaterials, [60]fullerenes displayed rapid extravasation from tumor vasculature, distinct from that in normal microvasculature. Temporal heterogeneity in fullerene delivery to tumors was observed, demonstrating the issue of nonuniform delivery beyond spatial dimensions. Trends in local region analysis of fullerene biokinetics by fluorescence quantification were in agreement with global image analysis. Further analysis of intratumoral vascular clearance rates suggested a possible enhanced penetration and retention effect of the fullerene compared to a 70 kDa vascular tracer. Overall, this study demonstrates the feasibility of tracking and quantifying the delivery kinetics and intratumoral biodistribution of fullerene-based drug delivery platforms, consistent with the EPR effect on short timescales and passive transport to tumors.Item Bismuth@US-tubes as a potential contrast agent for X-ray imaging applications(Royal Society of Chemistry, 2013) Rivera, Eladio J.; Tran, Lesa A.; Hernández-Rivera, Mayra; Yoon, Diana; Mikos, Antonios G.; Rusakova, Irene A.; Cheong, Benjamin Y.; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Wilson, Lon J.; Richard E. Smalley Institute for Nanoscale Science & TechnologyThe encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking.Item Bond activation by photoexcited metal atoms(1984) Gibbs, Suzanne; Billups, W. Edward; Parry, R. J.; Wilson, Lon J.This work involves a study of ground state and photoexcited metal atoms reacting with ethylene, cyclopropane, acetylene and ethylene oxide in an argon matrix at 12°K. The reactions were followed by infrared spectroscopy. Ground state titanium atoms deoxygenate ethylene oxide to yield TiO and ethylene. Both iron atoms and dimers form adducts with ethylene oxide which when photoexcited yield ethylene and the iron oxides. Whereas titanium atoms fail to react with cyclopropane, photoexcited iron atoms and dimers insert into a carboncarbon bond of cyclopropane. Photoexcited iron atoms also insert into a carbon-hydrogen bond of acetylene. Titanium atoms react spontaneously with acetylene to yield a complex. Titanium atoms react with ethylene to form either a three-membered ring or a dicarbene and higher complexes.Item Carbon and Silicon Nanomaterials for Medical Nanotechnology Applications(2015-05-18) Gizzatov, Ayrat; Wilson, Lon J.; Tour, James M; Vajtai, Robert; Decuzzi, PaoloThis 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.Item Carbon nanotube based imaging agents(2015-03-24) Wilson, Lon J.; Kissell, Kyle Ryan; Hartman, Keith Bennett; Rice University; United States Patent and Trademark OfficeCompositions and methods related to carbon nanotubes are provided. More particularly, imaging agents comprising carbon nanotubes internally loaded with a contrast agent and associated methods are provided. One example of a method may involve a method for imaging comprising: providing an imaging agent comprising a carbon nanotube loaded with contrast agent; introducing the imaging agent into a cell; and imaging the cell to detect the presence of the imaging agent.Item Carbon Nanotubides: an Alternative for Dispersion, Functionalization and Composites Fabrication(2016-04-14) Jiang, Chengmin; Marti, Angel A.; Pasquali, Matteo; Wilson, Lon J.Negatively charged single-walled carbon nanotube (SWCNT), also called SWCNT polyelectrolytes and single-walled carbon nanotubides (SWCNTDs), are formed by the reduction (either chemical or electrochemical) of the SWCNT wall by alkali metals (or an electrode) to form negative charged SWCNTs surrounded by an alkali metal counter ions. SWCNT polyelectrolytes can spontaneously dissolve in a variety of polar aprotic solvents without assistance of sonication and will readily react with alkyls and aryls halides to functionalize the walls of SWCNTs. Although SWCNT polyelectrolytes present a good alternative for achieving high concentration of SWCNTs in solution, the condensation of the counter ions on the surface of negatively charged SWCNTs partially shield their charge, limiting the solubility of SWCNT polyelectrolytes. For HiPco SWCNT polyelectrolytes, the highest solubility reported before this work was only 0.4 mg/mL in DMSO. However, we developed a method that greatly improve the solubility of SWCNTs by adding crown ether into the system to coordinate the potassium cation and thus separate the negatively charged SWCNTs from counter ions. This new method produces a high concentration of SWCNT polyelectrolytes up to 9.2 mg/mL in DMSO. In addition, we were able to observe the formation of liquid crystalline phases at highly concentrated solutions, which has been proved to be an essential factor for manufacturing highly ordered robust macroscopic materials. After applying a more efficient dispersion method, speed-mixing, the concentration of SWCNT polyelectrolytes can be further improved up to 52 mg/mL. Compared with previous reported results, the increase in solubility is more than 100 times. As mentioned above, we achieved high concentration of SWCNT polyelectrolytes by adding crown ether to the mixture and using speed-mixing. The SWCNTs in these solutions spontaneously align forming liquid crystalline solutions that can be manufactured into strong and conductive carbon nanotubes fibers by spinning the SWCNT dispersions into aqueous coagulation solutions. The best fibers we have obtained by this method have tensile strength up to 124 MPa, which compares to HiPco SWCNT fibers spun from superacid solutions, and conductivity 2 × 104 S/m. Our method provides an acid-free alternative towards high performance carbon nanotube fibers, which can be expanded for the production of other materials such as films. Also, we expanded our methodology to disperse graphite intercalation compounds (GICs) into graphene polyelectrolytes. Graphene polyelectrolytes, when mixed with SWCNT polyelectrolytes were spun onto SWCNT/Graphene hybrid fibers, which maintains a similar tensile strength (as for HiPco SWCNT fibers) while the Young’s modulus increases by 70% and conductivity increases 2 times.Item Carbon-Based Nanostructures as Advanced Contrast Agents for Magnetic Resonance Imaging(2011) Ananta Narayanan, Jeyarama Subramanian; Wilson, Lon J.Superparamagnetic carbon-based nanostructures are presented as contrast agents (CAs) for advanced imaging applications such as cellular and molecular imaging using magnetic resonance imaging (MRI). Gadolinium-loaded, ultra-short single-walled carbon nanotubes (gadonanotubes; GNTs) are shown to have extremely high rl relaxivities (contrast enhancement efficacy), especially at low-magnetic field strengths. The inherent lipophilicity of GNTs provides them the ability to image cells at low magnetic field strength. A carboxylated dextran-coated GNT (GadoDex) has been synthesized and proposed as a new biocompatible high-performance MRI CA. The rl relaxivity is ca. 20 times greater than for other paramagnetic Gd-based CAs. This enhanced relaxivity for GadoDex is due to the synergistic effects of an increased molecular tumbling time ('tR) and a faster proton exchange rate ('tm). GNTs also exhibit very large transverse relaxivities (r2) at high magnetic fields ~ 3 T). The dependence of the transverse relaxation rates (especially R2 *) of labeled cells on GNT concentration offers the possibility to quantify cell population in vivo using R2 * mapping. The cell-labeling efficiency and high transverse relaxivities of GNTs has enabled the first non-iron oxide-based single-cell imaging using MRI.Item Cisplatin@US-tube Carbon Nanocapsules for Enhanced(2014-02-28) Guven, Adem; Wilson, Lon J.; Colvin, Vicki L.; Barrera, Enrique V.; Lewis, Michael T.The use of chemotherapeutic drugs in cancer therapy is often limited by problems with administration such as insolubility, inefficient biodistribution, lack of selectivelty, and inability of the drug to cross cellular barriers. To overcome these limitations, various types of drug delivery systems have been explored, and recently, carbon nanotube (CNT) materials have garnered special attention in the area. This thesis details the preparation, characterization, and in vitro and in vivo testing of a new, ultra-short single-walled carbon nanotube (US-tube)-based drug delivery system for the treatment of cancer. In particular, the encapsulation of cisplatin (CDDP), a widely-used anticancer drug, within US-tubes has been achieved by a loading procedure that is reproducible, and the resulting CDDP@US-tube material characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), and inductively-coupled optical emission spectroscopy (ICP-OES). Dialysis studies performed in phosphate-buffered saline (PBS) at 37 °C have demonstrated that CDDP release from CDDP@US-tubes can be controlled (retarded) by wrapping the CDDP@US-tubes with Pluronic®-F108 surfactant. The anticancer activity of Pluronic-wrapped CDDP@US-tubes (W-CDDP@US-tubes) has been evaluated against two different breast cancer cell lines, MCF-7 and MDA-MB-231, and found to exhibit enhanced cytotoxicity over free CDDP. Moreover, it has been shown that CDDP release from W-CDDP@US-tubes nanocapsules can be stimulated remotely by a radiofrequency (RF) field which disrupts the Pluronic coating to release CDDP. RF-induced release-dependent cytotoxicity of W-CDDP@US-tubes has been evaluated in vitro against two different liver cancer cell lines, Hep3B and HepG2, and found to exhibit superior cytotoxicity compared to W-CDDP@US-tubes not exposed to RF. Finally, in vivo biodistribution and therapeutic efficacy of the CDDP@US-tube material has been evaluated against three different breast cancer xenograft mouse (SCID/Bg) models, and found to exhibit greater efficacy in suppressing tumor growth than free CDDP for both a MCF-7 cell line xenograft model and a BCM-4272 patient-derived xenograft (PDX) model. The CDDP@US-tubes also demonstrated prolonged circulation time compared to free CDDP which enhances permeability and retention (EPR) effects resulting in significantly more CDDP accumulation in tumors, as determined by Platinum (Pt) analysis via inductively-coupled plasma mass-spectrometry (ICP-MS).Item Citrate-Capped Gold Nanoparticle Electrophoretic Heat Production in Response to a Time-Varying Radio-Frequency Electric Field(American Chemical Society, 2012) Corr, Stuart J.; Raoof, Mustafa; Mackeyev, Yuri; Phounsavath, Sophia; Cheney, Matthew A.; Cisneros, Brandon T.; Shur, Michael; Gozin, Michael; McNally, Patrick J.; Wilson, Lon J.; Curley, Steven A.; Smalley Institute for Nanoscale Science and TechnologyThe evaluation of heat production from gold nanoparticles (AuNPs) irradiated with radio-frequency (RF) energy has been problematic due to Joule heating of their background ionic buffer suspensions. Insights into the physical heating mechanism of nanomaterials under RF excitations must be obtained if they are to have applications in fields such as nanoparticle-targeted hyperthermia for cancer therapy. By developing a purification protocol that allows for highly stable and concentrated solutions of citrate-capped AuNPs to be suspended in high-resistivity water, we show herein, for the first time, that heat production is only evident for AuNPs of diameters ≤10 nm, indicating a unique size-dependent heating behavior not previously observed. Heat production has also shown to be linearly dependent on both AuNP concentration and total surface area and was severely attenuated upon AuNP aggregation. These relationships have been further validated using permittivity analysis across a frequency range of 10 MHz–3 GHz as well as static conductivity measurements. Theoretical evaluations suggest that the heating mechanism can be modeled by the electrophoretic oscillation of charged AuNPs across finite length scales in response to a time-varying electric field. It is anticipated these results will assist future development of nanoparticle-assisted heat production by RF fields for applications such as targeted cancer hyperthermia.Item Cytotoxicity and variant cellular internalization behavior of water-soluble sulfonated nanographene sheets in liver cancer cells(Springer, 2013) Corr, Stuart J.; Raoof, Mustafa; Cisneros, Brandon T.; Kuznetsov, Oleksandr; Massey, Katheryn; Kaluarachchi, Warna D.; Cheney, Matthew A.; Billups, Edward W.; Wilson, Lon J.; Curley, Steven A.; Richard E. Smalley Institute for Nanoscale Science and TechnologyHighly exfoliated sulfonated graphene sheets (SGSs), an alternative to graphene oxide and graphene derivatives, were synthesized, characterized, and applied to liver cancer cells in vitro. Cytotoxicity profiles were obtained using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, WST-1[2-(4-iodophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, and lactate dehydrogenase release colorimetric assays. These particles were found to be non-toxic across the concentration range of 0.1 to 10 μg/ml. Internalization of SGSs was also studied by means of optical and electron microscopy. Although not conclusive, high-resolution transmission and scanning electron microscopy revealed variant internalization behaviors where some of the SGS became folded and compartmentalized into tight bundles within cellular organelles. The ability for liver cancer cells to internalize, fold, and compartmentalize graphene structures is a phenomenon not previously documented for graphene cell biology and should be further investigated.Item 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 Technology225Ac3+ 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.Item 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 TechnologyThe 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.Item 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 NanotechnologyGadolinium 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.Item Evidence for nuclear internalisation of biocompatible [60]fullerene1)(Walter de Gruyter GmbH, 2013) Huang, Feiran; Mackeyev, Yuri; Watson, Erin; Cheney, Matthew A.; Wilson, Lon J.; Suh, Junghae; Richard E. Smalley Institute for Nanoscale Science and TechnologyMany types of nanoparticles (NPs) have been shown to internalise within mammalian cells (1), but only a few have been observed to internalise within the cell nucleus-most likely due to the tightly-regulated nuclear membrane (2). Internalisation of NPs into the nucleus is desirable for several reasons, including their use as 1. transfection agents (3), 2. drug delivery platforms for drugs that act on DNA (4), and 3. hyperthermia-inducing agents for cancer therapy using non-invasive stimulation by radiofrequency irradiation (5), magnetic-field cycling (6), or photonic activation (7). For example, derivatised NPs, including protein-functionalised quantum dots (8) and peptide-functionalised gold NPs (9), have been shown to internalise into the nucleus. For underivatised NPs, single-walled carbon nanotubes (SWNTs), have been observed by direct transmission electron microscopy (TEM) imaging to also localise in the nucleus of human macrophage cells with dose-dependent cytotoxicity (10). Fullerene C60ﾠis another classic carbon-based NP, however it was not been shown to enter the cell nucleus until recently. In particular, a water soluble derivative of C60ﾠfluorescently labelled with a small molecule fluorophore was shown to enter cell nuclei through nuclear pore complexes in liver cancer cells (11). Here, we validate the nuclear internalisation ability of the C60derivative in several other cell types, further supporting the unique intracellular biodistribution property of this specific fullerene compound.