Browsing by Author "Corr, Stuart J."

Now showing 1 - 9 of 9
  • Thumbnail Image
    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.
  • Thumbnail Image
    Item
    Cadaveric aortic aneurysm creation: A life-like model for training endovascular repair
    (Elsevier, 2023) Osztrogonacz, Peter; Benfor, Bright; Haddad, Paul; Barnes, Rebecca; Chinnadurai, Ponraj; Dang, Vy; Hess, John Paul; Corr, Stuart J.; Rahimi, Maham
    The recent decline in RAAA incidence and the fast paced scenario with associated challenges regarding training calls for initiative for a better training environment to maximize learning. This led us to the creation of a pulsatile human cadaveric RAAA model. Fresh frozen cadaver was used to create RAAA with BioTissue in hybrid suite with ability to perform CBCTA for sizing. As a proof of concept, the model was used to perform REVAR with proximal CODA balloon control. The model proved to be feasible and we believe it is a better environment to train and gain adequate proficiency in RAAA management.
  • Thumbnail Image
    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 Technology
    The 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.
  • Thumbnail Image
    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 Technology
    Highly 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.
  • Thumbnail Image
    Item
    Gold nanoparticles and radiofrequency in experimental models for hepatocellular carcinoma
    (Elsevier, 2014) Raoof, Mustafa; Corr, Stuart J.; Zhu, Cihui; Cisneros, Brandon T.; Kaluarachchi, Warna D.; Phounsavath, Sophia; Wilson, Lon J.; Curley, Steven A.; Richard E. Smalley Institute for Nanoscale Science & Technology
    Hepatocellular carcinoma (HCC) is one of the most lethal and chemo-refractory cancers, clearly, alternative treatment strategies are needed. We utilized 10 nm gold nanoparticles as a scaffold to synthesize nanoconjugates bearing a targeting antibody (cetuximab, C225) and gemcitabine. Loading efficiency of gemcitabine on the gold nanoconjugates was 30%. Targeted gold nanoconjugates in combination with RF were selectively cytotoxic to EGFR expressing Hep3B and SNU449 cells when compared to isotype particles with/without RF (P < 0.05). In animal experiments, targeted gold nanoconjugates halted the growth of subcutaneous Hep3B xenografts in combination with RF exposure (P < 0.05). These xenografts also demonstrated increased apoptosis, necrosis and decreased proliferation compared to controls. Normal tissues were unharmed. We have demonstrated that non-invasive RF-induced hyperthermia when combined with targeted delivery of gemcitabine is more effective and safe at dosages ~ 275-fold lower than the current clinically-delivered systemic dose of gemcitabine.
  • Thumbnail Image
    Item
    Gold Nanoparticles Stabilized with MPEG-Grafted Poly(l-lysine): in Vitro and in Vivo Evaluation of a Potential Theranostic Agent
    (American Chemical Society, 2015) Bogdanov, Alexei A. Jr.; Gupta, Suresh; Koshkina, Nadezhda; Corr, Stuart J.; Zhang, Surong; Curley, Steven A.; Han, Gang
    As the number of diagnostic and therapeutic applications utilizing gold nanoparticles (AuNPs) increases, so does the need for AuNPs that are stable in vivo, biocompatible, and suitable for bioconjugation. We investigated a strategy for AuNP stabilization that uses methoxypolyethylene glycol-graft-poly(l-lysine) copolymer (MPEG-gPLL) bearing free amino groups as a stabilizing molecule. MPEG-gPLL injected into water solutions of HAuCl4 with or without trisodium citrate resulted in spherical (Zav = 36 nm), monodisperse (PDI = 0.27), weakly positively charged nanoparticles (AuNP3) with electron-dense cores (diameter: 10.4 ± 2.5 nm) and surface amino groups that were amenable to covalent modification. The AuNP3 were stable against aggregation in the presence of phosphate and serum proteins and remained dispersed after their uptake into endosomes. MPEG-gPLL-stabilized AuNP3 exhibited high uptake and very low toxicity in human endothelial cells, but showed a high dose-dependent toxicity in epithelioid cancer cells. Highly stable radioactive labeling of AuNP3 with 99mTc allowed imaging of AuNP3 biodistribution and revealed dose-dependent long circulation in the blood. The minor fraction of AuGNP3 was found in major organs and at sites of experimentally induced inflammation. Gold analysis showed evidence of a partial degradation of the MPEG-gPLL layer in AuNP3 particles accumulated in major organs. Radiofrequency-mediated heating of AuNP3 solutions showed that AuNP3 exhibited heating behavior consistent with 10 nm core nanoparticles. We conclude that PEG-pPLL coating of AuNPs confers “stealth” properties that enable these particles to exist in vivo in a nonaggregating, biocompatible state making them suitable for potential use in biomedical applications such as noninvasive radiofrequency cancer therapy.
  • Thumbnail Image
    Item
    Intravital microscopy for evaluating tumor perfusion of nanoparticles exposed to non-invasive radiofrequency electric fields
    (Springer, 2016) Lapin, Norman A.; Krzykawska-Serda, Martyna; Ware, Matthew J.; Curley, Steven A.; Corr, Stuart J.
    Poor biodistribution and accumulation of chemotherapeutics in tumors due to limitations on diffusive transport and high intra-tumoral pressures (Jain RK, Nat Med. 7(9):987–989, 2001) have prompted the investigation of adjunctive therapies to improve treatment outcomes. Hyperthermia has been widely applied in attempts to meet this need, but it is limited in its ability to reach tumors in deeply located body regions. High-intensity radiofrequency (RF) electric fields have the potential to overcome such barriers enhancing delivery and extravasation of chemotherapeutics. However, due to factors, including tumor heterogeneity and lack of kinetic information, there is insufficient understanding of time-resolved interaction between RF fields and tumor vasculature, drug molecules and nanoparticle (NP) vectors. Intravital microscopy (IVM) provides time-resolved high-definition images of specific tumor microenvironments, overcoming heterogeneity issues, and can be integrated with a portable RF device to enable detailed observation over time of the effects of the RF field on kinetics and biodistribution at the microvascular level. Herein, we provide a protocol describing the safe integration of IVM with a high-powered non-invasive RF field applied to 4T1 orthotopic breast tumors in live mice. Results show increased perfusion of NPs in microvasculature upon RF hyperthermia treatment and increased perfusion, release and spreading of injected reagents preferentially in irregular vessels during RF exposure.
  • Thumbnail Image
    Item
    Remotely triggered cisplatin release from carbon nanocapsules by radiofrequency fields
    (Elsevier, 2013) Raoof, Mustafa; Cisneros, Brandon T.; Guven, Adem; Corr, Stuart J.; Wilson, Lon J.; Curley, Steven A.; Richard E. Smalley Institute for Nanoscale Science & Technology
    The efficacy of nanoparticle-mediated drug delivery is limited by its peri-vascular sequestration, thus necessitating a strategy to trigger drug release from such intra-tumoral nanocarrier-drug depots. In our efforts to explore remotely-activated nanocarriers, we have developed carbon nanocapsules comprised of an ultra-short carbon nanotube shell (US-tubes) loaded with cisplatin (CDDP@US-tubes) and covered with a Pluronic surfactant wrapping to minimize passive release. We demonstrate here that non-invasive radiofrequency (RF) field activation of the CDDP@US-tubes produces heat that causes Pluronic disruption which triggers cisplatin release in an RF-dependent manner. Furthermore, release-dependent cytotoxicity is demonstrated in human hepatocellular carcinoma cell lines.
  • Thumbnail Image
    Item
    Water-structuring molecules and nanomaterials enhance radiofrequency heating in biologically relevant solutions
    (Royal Society of Chemistry, 2016) Lara, Nadia C.; Haider, Asad A.; Ho, Jason C.; Wilson, Lon J.; Barron, Andrew R.; Curley, Steven A.; Corr, Stuart J.
    For potential applications in nano-mediated radiofrequency cancer hyperthermia, the nanomaterial under investigation must increase the heating of any aqueous solution in which it is suspended when exposed to radiofrequency electric fields. This should also be true for a broad range of solution conductivities, especially those that artificially mimic the ionic environment of biological systems. Herein we demonstrate enhanced heating of biologically relevant aqueous solutions using kosmotropes and a hexamalonoserinolamide fullerene.