Browsing by Author "Mackeyev, Yuri"
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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 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 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.Item Facile purification of carbon nanotubes with liquid bromine at room temperature(2012-03-06) Mackeyev, Yuri; Wilson, Lon J.; Rice University; United States Patent and Trademark OfficeA method of removing metal impurities from carbon nanotubes includes treating carbon nanotubes with distilled bromine in a substantially oxygen- and water-free atmosphere and then removing the distilled bromine from the carbon nanotubes. Purified carbon nanotubes having an iron content from about 2.5 to about 3.5 by weight that are substantially free of derivatization at the ends and defect sites are made available via this method.Item Fullerene compositions and methods for photochemical purification(2014-03-25) Alvarez, Pedro J.J.; Lee, Jaesang; Wilson, Lon J.; Mackeyev, Yuri; Kim, Jaehong; Rice University; Georgia Tech Research Corporation; United States Patent and Trademark OfficeIn various embodiments, the present disclosure describes fullerene derivatives that are capable of photocatalytically generating reactive oxygen species in the presence of ultraviolet and/or visible light. In some embodiments, the fullerene derivatives are aminofullerenes containing a plurality of amine-terminated moieties covalently bonded to the fullerene cage. The fullerene derivatives may optionally be covalently bonded to a substrate surface for use in photocatalytic disinfection systems for removing various contaminants including, for example, bacteria, viruses, protozoa and chemical pollutants. Methods using the present fullerene and aminofullerene derivatives in various purification processes are also described herein.Item Pancreatic tumor microenvironmental acidosis and hypoxia transform gold nanorods into cell-penetrant particles for potent radiosensitization(AAAS, 2022) Rauta, Pradipta Ranjan; Mackeyev, Yuri; Sanders, Keith; Kim, Joseph B.K.; Gonzalez, Valeria V.; Zahra, Yasmin; Shohayeb, Muhammad A.; Abousaida, Belal; Vijay, Geraldine V.; Tezcan, Okan; Derry, Paul; Liopo, Anton V.; Zubarev, Eugene R.; Carter, Rickey; Singh, Pankaj; Krishnan, SunilCoating nanoparticles with stealth epilayers increases circulation time by evading opsonization, macrophage phagocytosis, and reticuloendothelial sequestration. However, this also reduces internalization by cancer cells upon reaching the tumor. We designed gold nanorods (GNRs) with an epilayer that retains stealth properties in circulation but transforms spontaneously in the acidotic tumor microenvironment to a cell-penetrating particle. We used a customized stoichiometric ratio of l-glutamic acid and l-lysine within an amphiphilic polymer of poly(l-glutamic acid-co-l-lysine), or P(Glu-co-Lys), to effect this transformation in acidotic environments. P(Glu-co-Lys)-GNRs were internalized by cancer cells to facilitate potent in vitro radiosensitization. When administered intravenously in mice, they accumulate in the periphery and core of tumors without any signs of serum biochemical or hematological alterations, normal organ histopathological abnormalities, or overt deterioration in animal health. Furthermore, P(Glu-co-Lys)-GNRs penetrated the tumor microenvironment to accumulate in the hypoxic cores of tumors to potently radiosensitize heterotopic and orthotopic pancreatic cancers in vivo.Item 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 TechnologyThere 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.