Ferenc Horkay

Eunice Kennedy Shriver National Institute of Child Health and Human Development, Роквилл, Maryland, United States

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Publications (226)609.43 Total impact

  • F. Horkay · P. J. Basser · A.-M. Hecht · E. Geissler ·

    Proceedings of the Institution of Mechanical Engineers Part H Journal of Engineering in Medicine 12/2015; 229(12):895-904. DOI:10.1177/0954411915602915 · 1.33 Impact Factor
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    ABSTRACT: Despite the effort of developing various nanodelivery systems, most of them suffer from undesired high uptakes by the reticuloendothelial system, such as liver and spleen. Herein we develop an endogenous phosphatase-triggered coassembly strategy to form tumor-specific indocyanine green (ICG)-doped nanofibers (5) for cancer theranostics. Based on coordinated intermolecular interactions, 5 significantly altered near-infrared absorbance of ICG, which improves the critical photoacoustic and photothermal properties. The phosphatase-instructed coassembly process, as well as its theranostic capability, was successfully conducted at different levels ranging from in vitro, living cell, tissue mimic, to in vivo. Specifically, the tumor uptake of ICG was markedly increased to 15.05 ± 3.78%ID/g, which was 25-fold higher than that of free ICG (0.59 ± 0.24%ID/g) at 4 h after intravenous injection. The resulting ultrahigh T/N ratios (>15) clearly differentiated tumors from the surrounding normal tissue. Complete tumor elimination with high therapeutic accuracy has been successfully achieved upon laser irradiation (0.8 W/cm(2), 5 min) within 24-48 h postinjection. As the first example, in vivo formation of tumor-specific ICG-doped nanofiber for PTT theranostics owns the immense potential for clinical translation of personalized nanomedicine with targeted drug delivery as well as for cancer theranostics.
    ACS Nano 08/2015; DOI:10.1021/acsnano.5b03874 · 12.88 Impact Factor
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    ABSTRACT: Since the celebration of the 20th anniversary of the first heart transplantation in Hungary in 2012 the emerging need for modern heart failure management via mechanical circulatory support has evolved. In May 2012 the opening of a new heart failure and transplant unit with 9 beds together with the procurement of necessary devices at Semmelweis University accomplished this need. The aim of the authors was to report their initial experience obtained in this new cardiac assist device program. Since May, 2012, mechanical circulatory support system was applied in 89 cases in 72 patients. Indication for support were end stage heart failure refractory to medical treatment and acute left or right heart failure. Treatment was initiated for acute graft failure after heart transplantation in 27 cases, for end stage heart failure in 24 cases, for acute myocardial infarction in 21 cases, for acute postcardiotomy heart failure in 14 cases, for severe respiratory insufficiency in 2 cases and for drug intoxication in one case. Among the 30 survivor of the whole program 13 patients were successfully transplanted. The available devices can cover all modalities of current bridge therapy from short term support through medium support to heart transplantation or long term support and destination therapy. These conditions made possible the successful start of a new cardiac assist device program. Orv. Hetil., 2015, 156(13), 521-527.
    Orvosi Hetilap 03/2015; 156(13):521-527. DOI:10.1556/OH.2015.30115
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    ABSTRACT: Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate nanoparticles of DNA that can be targeted to the antigen-presenting cells of the immune system. We report that the sugar modification alters the DNA organization within the nanoparticles from homogenous to shell-like packing. The depth-dependent packing of DNA within the nanoparticles was probed using AFM nano-indentation. Unmodified PEI-DNA nanoparticles display linear elastic properties and depth-independent mechanics, characteristic of homogenous materials. Mannobiose-modified nanoparticles, however, showed distinct force regimes that were dependent on indentation depth, with 'buckling'-like response that is reproducible and not due to particle failure. By comparison with theoretical studies of spherical shell mechanics, the structure of mannobiosylated particles was deduced to be a thin shell with wall thickness in the order of few nanometers, and a fluid-filled core. The shell-core structure is also consistent with observations of nanoparticle denting in altered solution conditions, with measurements of nanoparticle water content from AFM images, and with images of DNA distribution in Transmission Electron Microscopy.
    Soft Matter 08/2014; 10(38). DOI:10.1039/c4sm00908h · 4.03 Impact Factor
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    ABSTRACT: There is no clinically available cancer immunotherapy that exploits Langerhans cells (LCs), the epidermal precursors of dendritic cells (DCs) that are the natural agent of antigen delivery. We developed a DNA formulation with a polymer and obtained synthetic 'pathogen-like' nanoparticles that preferentially targeted LCs in epidermal cultures. These nanoparticles applied topically under a patch-elicited robust immune responses in human subjects. To demonstrate the mechanism of action of this novel vaccination strategy in live animals, we assembled a high-resolution two-photon laser scanning-microscope. Nanoparticles applied on the native skin poorly penetrated and poorly induced LC motility. The combination of nanoparticle administration and skin treatment was essential both for efficient loading the vaccine into the epidermis and for potent activation of the LCs to migrate into the lymph nodes. LCs in the epidermis picked up nanoparticles and accumulated them in the nuclear region demonstrating an effective nuclear DNA delivery in vivo. Tissue distribution studies revealed that the majority of the DNA was targeted to the lymph nodes. Preclinical toxicity of the LC-targeting DNA vaccine was limited to mild and transient local erythema caused by the skin treatment. This novel, clinically proven LC-targeting DNA vaccine platform technology broadens the options on DC-targeting vaccines to generate therapeutic immunity against cancer.Gene Therapy advance online publication, 3 April 2014; doi:10.1038/gt.2014.29.
    Gene therapy 04/2014; 21(6). DOI:10.1038/gt.2014.29 · 3.10 Impact Factor

  • 247th National Spring Meeting of the American-Chemical-Society (ACS); 03/2014
  • Ruiliang Bai · Peter J. Basser · Robert M. Briber · Ferenc Horkay ·
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    ABSTRACT: Water self-diffusion coefficients and longitudinal relaxation rates in sodium polyacrylate solutions and gels were measured by NMR, as a function of polymer content and structure in a physiological concentration range of monovalent and divalent cations, Ca2+ and Na+. Several physical models describing the self-diffusion of the solvent were applied and compared. A free-volume model was found to be in good agreement with the experimental results over a wide range of polymer concentrations. The longitudinal relaxation rate exhibited linear dependence on polymer concentration below a critical concentration and showed non-linear behavior at higher concentrations. Both the water self-diffusion and relaxation were less influenced by the polymer in the gel state than in the uncrosslinked polymer solutions. The effect of Na+ on the mobility of water molecules was practically undetectable. In contrast, addition of Ca2+ strongly increased the longitudinal relaxation rate while its effect on the self-diffusion coefficient was much less pronounced. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014, 131, 40001.
    Journal of Applied Polymer Science 03/2014; 131(6). DOI:10.1002/app.40001 · 1.77 Impact Factor

  • MRS Online Proceeding Library 01/2014; 1622. DOI:10.1557/opl.2014.73
  • Dan Benjamini · Uzi Eliav · Uri Nevo · Peter J. Basser · Ferenc Horkay ·
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    ABSTRACT: It is biologically and clinically important to understand and explain the functional properties of cartilage, such as its load bearing and lubricating ability, in terms of the structure, organization, components and their interactions. Our approach tries to explain functional material properties of these tissues as arising from polymeric interactions between and among the different molecular constituents within the tissues at different hierarchical lengthscales. We treat the tissue effectively as a complex molecular composite containing highly charged polysaccharide microgels trapped within a fine collagen meshwork. We have been developing a multi-scale experimental and theoretical framework to explain key material properties of cartilage by studying those of its constituents and the interactions among them at a variety of length and time scales. We use this approach to address important biological questions. One novel application we highlight here is the use of non-invasive magnetic resonance imaging (MRI) methods to characterize different components and compartments within cartilage and the different water environments associated with each one, in an attempt to provide a comprehensive picture of the mechanical/chemical state of cartilage.
    MRS Online Proceeding Library 01/2014; 1622. DOI:10.1557/opl.2014.361
  • Hacène Boukari · Candida Silva · Ralph Nossal · Ferenc Horkay ·

    MRS Online Proceeding Library 01/2014; 1622. DOI:10.1557/opl.2014.74
  • Chinedu I. Anyaeji · Peter J. Basser · Ferenc Horkay ·
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    ABSTRACT: Cartilage is a complex biological tissue that exhibits gel-like behavior. Its primary biological function is providing compressive resistance to external loading and nearly frictionless lubrication of joints. In this study, we model cartilage extracellular matrix using a biomimetic system. We demonstrate that poly(vinyl) alcohol (PVA) hydrogels are robust biomaterials exhibiting mechanical and swelling properties similar to that of cartilage extracellular matrix. A comparison is made between the macroscopic behavior of PVA gels and literature data reported for cartilage.
    MRS Online Proceeding Library 01/2014; 1622. DOI:10.1557/opl.2014.55
  • Yuan Gao · Yi Kuang · Xuewen Du · Jie Zhou · Preethi Chandran · Ferenc Horkay · Bing Xu ·
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    ABSTRACT: Self-assembly of small molecules, as a more common phenomenon than one previously thought, can be either beneficial or detrimental to cells. Despite its profound biological implications, how the self-assembly of small molecules behave in cellular environment is largely unknown and barely explored. This work studies four fluorescent molecules that consist of the same peptidic backbone (e.g., Phe-Phe-Lys) and enzyme trigger (e.g., a phosphotyrosine residue), but bear different fluorophores on the side chain of the lysine residue of the peptidic motif. These molecules, however, exhibit different ability of self-assembly before and after enzymatic transformation (e.g., dephosphorylation). Fluorescent imaging reveals that self-assembly directly affects the distribution of these small molecules in cellular environment. Moreover, cell viability tests suggest that the states and the location of the molecular assemblies in the cellular environment control the phenotypes of the cells. For example, the molecular nanofibers of one of the small molecules apparently stabilize actin filaments and alleviate the insult of an F-actin toxin (e.g., latrunculin A). Combining fluorescent imaging and enzyme-instructed self-assembly of small peptidic molecules, this work, for the first time, not only demonstrates that self-assembly as a key factor for dictating the spatial distribution of small molecules in cellular environment, but also illustrates a useful approach, based on enzyme-instructed self-assembly of small molecules, to modulate spatiotemporal profiles of small molecules in cellular environment for using the emergent properties of small molecules to control the fate of cells.
    Langmuir 11/2013; 29(49). DOI:10.1021/la403457c · 4.46 Impact Factor
  • Ferenc Horkay ·
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    ABSTRACT: Systematic investigations using small angle neutron scattering (SANS) were made to reveal the effect of calcium ions on the structure of DNA gels and solutions in near-physiological salt solutions. To describe the neutron scattering response two characteristic distances are required. The shorter length scale, R (≈10 Å), was found to be governed by the geometry of the DNA chain and is close to the cross-sectional radius of the double helix. The longer length scale L corresponds to the mesh size of the network of overlapping polymer chains. L decreases with increasing DNA concentration as L ∝ cDNA−0.73. With increasing CaCl2 concentration both L and the scattering intensity increase. The increase in the scattering intensity reflects the reduction of the osmotic modulus as the calcium ion concentration increases. The values of the osmotic modulus derived from osmotic swelling pressure measurements are in reasonable agreement with those obtained from SANS.
    Macromolecular Symposia 07/2013; 329(1). DOI:10.1002/masy.201300028
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    ABSTRACT: The Hungarian adult heart transplant program, which started in 1992, has changed gradually in the past 20 years. After the early enthusiasm of the first cases it changed significantly and it became an organized programme. However, low donation activity and moderate referral numbers to the national transplant waiting list slowed down the process therefore, heart transplant numbers did not fulfill expectations in the early years. After a moderate increase in 2007 transplant numbers have dropped again until recently when Hungary partially joined Eurotransplant network. Excess fundamental resources allocated to cardiac transplantation by health care professionals and reorganizing transplant coordination as well as logistics forced dramatic changes in clinical management. In 2011 and 2012 major structural changes had been made at Semmelweis University. The newly established transplant intensive care unit and the initiation of mechanical circulatory support and assist device programme increased transplant numbers by 131% compared to previous years, as well as it resulted an 86.63% 30-day survival rate, hence last year was the most successful year of cardiac transplantation ever. Orv. Hetil., 2013, 154, 863-867.
    Orvosi Hetilap 06/2013; 154(22):863-867. DOI:10.1556/OH.2013.29622
  • Ferenc Horkay ·
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    ABSTRACT: This chapter contains sections titled: Introduction Basic Principles of SANS Experimental Examples Proteins Polynucleic Acids (DNA and RNA) Polysaccharide-Based Biopolymers Summary References
    Handbook of Biopolymer-Based Materials, 04/2013: pages 583-610; , ISBN: 9783527328840
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    ABSTRACT: Knowledge of microstructural features of nerve fascicles, such as their axon diameter, is crucial for understanding normal function in the central and peripheral nervous systems as well as assessing changes due to pathologies. In this study double-pulsed field gradient (d-PFG) filtered MRI was used to map the average axon diameter (AAD) in porcine spinal cord, which was then compared to AADs measured with optical microscopy of the same specimen, as a way to further validate this new MRI method. A novel 3D d-PFG acquisition scheme was used to obtain AADs in each voxel of a coronal slice of rat brain corpus callosum. AAD measurements were also acquired using optical microscopy performed on histological sections and validated using a glass capillary array phantom.
    NeuroImage 04/2013; 78. DOI:10.1016/j.neuroimage.2013.03.074 · 6.36 Impact Factor
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    ABSTRACT: Storage protocols of vascular grafts need further improvement against ischemia/reperfusion (IR)-injury. Hypoxia elicits a variety of complex cellular responses by altering the activity of many signalling pathways, such as the oxygen-dependent prolyl-hyroxylase-domain containing enzyme (PHD). Reduction of PHD-activity during hypoxia leads to stabilisation and accumulation of hypoxia inducible factor (HIF) 1α. We examined the effects of PHD-inhibiton by dimethyloxalylglycine on the vasomotor responses of isolated rat aorta and aortic vascular smooth muscle cells (VSMC) in a model of cold ischemia/warm reperfusion. Aortic segments underwent 24h cold ischemic preservation in saline or DMOG-supplemented saline solution. We investigated endothelium-dependent and -independent vasorelaxations. To simulate IR-injury hypochlorite (NaOCl) was added during warm reperfusion. VSMCs were incubated in NaCl or DMOG solution at 4°C for 24h after the medium was changed for a supplied standard medium at 37°C for 6h. Apoptosis was assessed by the TUNEL-method. Gene expression analysis was performed by quantitative real-time PCR. Cold ischemic preservation + NaOCl induced severe endothelial dysfunction, which was significantly improved by DMOG supplementation (maximal relaxation of aortic segments to acetylcholine: control 95±1 vs. NaOCl 44±4 vs. DMOG 68±5%). Number of TUNEL-positive cell nuclei was significantly higher in the NaOCl-group and DMOG-treatment significantly decreased apoptosis. Inducible heme-oxygenase 1 mRNA expressions were significantly higher in the DMOG group. Pharmacological modulation of oxygen sensing system by DMOG in an in vitro model of vascular IR effectively preserved endothelial function. Inhibition of PHDs could be therefore a new therapeutic avenue for protecting endothelium and vascular muscle cells against IR-injury.
    Journal of Pharmacology and Experimental Therapeutics 02/2013; 345(1). DOI:10.1124/jpet.112.200790 · 3.97 Impact Factor
  • Source
    Hacene Boukari · Candida de Silva · Ralph Nossal · Ferenc Horkay ·

    Biophysical Journal 01/2013; 104(2):349-. DOI:10.1016/j.bpj.2012.11.1937 · 3.97 Impact Factor
  • Ferenc Horkay ·
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    ABSTRACT: Articular cartilage is a low-friction, load-bearing tissue located at joint surfaces. The extracellular matrix (ECM) of cartilage consists of a fibrous collagen network, which is pre-stressed by the osmotic swelling pressure exerted by negatively charged proteoglycan aggregates embedded in the collagen network. The major proteoglycan is the bottlebrush shaped aggrecan, which forms complexes with linear hyaluronic acid chains. We quantify microscopic and macroscopic changes resulting from self-assembly between aggrecan and hyaluronic acid using a complementary set of physical measurements to determine structure and interactions by combining scattering techniques, including small-angle X-ray scattering, small-angle neutron scattering, and dynamic light scattering with macroscopic osmotic pressure measurements. It is demonstrated that the osmotic pressure that defines the load bearing ability of cartilage is primarily governed by the main macromolecular components (aggrecan and collagen) of the ECM. Knowledge of the interactions between the macromolecular components of cartilage ECM is essential to understand biological function and to develop successful tissue engineering strategies for cartilage repair.
    Journal of Polymer Science Part B Polymer Physics 12/2012; 50(24):1699-1705. DOI:10.1002/polb.23191 · 3.83 Impact Factor
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    ABSTRACT: In earlier studies severe ventricular arrhythmias developed during intrapericardial (i.p.) endothelin-1 (ET-1) infusion. Monophasic action potential duration (MAPD90) increase and significant ST segment elevation preceded the onset of arrhythmias. The aim of this study was to test the antiarrhythmic and antiischemic efficacy of the mixed endothelin-A- and -B- (ETA/B) receptor antagonist bosentan (BOS) on ET-1-induced arrhythmias on six mongrel dogs. Ten minutes after an intravenous bolus dose of BOS (10 mg/kg), ET-1 (33 pmol/kg/min) was given into the pericardial space for 30 min (BOS group). Six control dogs received only ET-1 infusion (control group). Mean arterial blood pressure (MAP), cardiac output, electrocardiograph (ECG), right and left ventricular endo- and epicardial (RVEND, RVEP, LVEND, LVEP) MAPD90s were recorded. MAP and cardiac output did not change significantly in the BOS group. Significant MAPD90 prolongation was found in all investigated regions of the control group (ET start vs ET 20 min: LVEP, 174 +/- 3 vs 208 +/- 10*; RVEND, 206 +/- 9 vs 241 +/- 12* ms, *p < 0.05), while significant MAPD90 alterations were not observed in the BOS group (basic vs ET 20 min: RVEP, 189 +/- 5 vs 196 +/- 5; LVEP, 199 +/- 5 vs 199 +/- 4; RVEND, 194 +/- 5 vs 195 +/- 6; LVEND, 209 +/- 3 vs 213 +/- 5 ms). Early afterdepolarizations (EADs) were observed in three control dogs. Severe ventricular arrhythmias [incessant nonsustained ventricular tachycardias (nsVTs) in all cases, sustained VTs (sVTs) in four, ventricular fibrillation (VF) in two instances] were present in the control group, whereas nsVTs were observed only in two dogs in the BOS group. ST segment elevation was more pronounced in the control group than in the BOS group (1.01 +/- 0.2 vs 0.41 +/- 0.07 mV, p < 0.05). In summary, bosentan effectively inhibits intrapericardial ET-1-induced ventricular arrhythmias, moreover it may have a protective effect against epimyocardial ischemia.
    Journal of Cardiovascular Pharmacology 08/2012; 36(Supplement 1). DOI:10.1097/00005344-200036051-00093 · 2.14 Impact Factor

Publication Stats

4k Citations
609.43 Total Impact Points


  • 2001-2015
    • Eunice Kennedy Shriver National Institute of Child Health and Human Development
      Роквилл, Maryland, United States
  • 2000-2014
    • National Institutes of Health
      • Section on Tissue Biophysics and Biomimetics
      Maryland, United States
    • National Institute for Food and Nutrition Science
      Budapeŝto, Budapest, Hungary
  • 1997-2013
    • Semmelweis University
      • • Department of Vascular Surgery
      • • Department of Cardiac Surgery
      Budapeŝto, Budapest, Hungary
  • 2002-2008
    • National Institute of Child Health and Human Development
      Maryland, United States
  • 2005
    • National Eye Institute
      베서스다, Maryland, United States
  • 2004
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1990-2001
    • University of Grenoble
      Grenoble, Rhône-Alpes, France
  • 1989-1997
    • University Joseph Fourier - Grenoble 1
      • Laboratoire Interdisciplinaire de Physique
      Grenoble, Rhône-Alpes, France
  • 1988-1997
    • Eötvös Loránd University
      Budapeŝto, Budapest, Hungary
  • 1994-1996
    • National Institute of Standards and Technology
      • Polymers Division
      GAI, Maryland, United States
  • 1993-1994
    • University of Freiburg
      Freiburg, Baden-Württemberg, Germany
  • 1991-1992
    • Institut Laue-Langevin
      Grenoble, Rhône-Alpes, France
    • Universität Ulm
      Ulm, Baden-Württemberg, Germany
  • 1986
    • Hungarian Academy of Sciences
      Budapeŝto, Budapest, Hungary
  • 1980-1982
    • The National Institute of Child Health, Budapest
      Budapeŝto, Budapest, Hungary