Giorgio, Todd D.Research Information
Professor and Chair of Biomedical Engineering
Professor of Chemical and Biomolecular Engineering
Professor of Cancer Biology
1. Nonviral Gene Delivery and TherapyOur lab has quantitatively assessed nonviral gene therapy for over 10 years. We remain interested in designing nanomaterials and methods to overcome the obstacles of gene delivery for human therapy. Our approach depends on quantitative characterization of the extracellular and intracellular events that control gene delivery and expression. A recent paper described the effects of simulated cardiovascular flow on lipoplex delivery to the cell surface through both modeling and experiment.
2. Drug Delivery Systems and DiagnosticsMuch of our current activities in this area are based on the synthesis and characterization of multifunctional nanoscale materials.
2a. Proximity Activated TargetingTranslation of single-mode molecular targeting strategies from in vitro models to in vivo applications has largely been unsuccessful. Our approach is to conceal a conventional molecular target bound to the surface of a nanoparticle with a masking agent that can be cleaved in the proximity of the target tissue. In this way, two events are required for targeted delivery: simultaneous availability of the agent that reveals the normally concealed ligand and the cell surface receptor. This approach requires the physical colocalization of both events, provided by a nanoparticle in our current work.
2b. Magnetically Directed VehiclesNew developments in nanoscale material science, biomaterials and medical imaging offer materials and methods that may generate magnetic approaches suitable for clinical application. Our laboratory has been exploring the quantitative assessment of superparamagnetic (SPM) nanoparticle (NP) motion in simulated extracellular matrix (ECM). Our approach includes surface functionalization of the SPM NP with a proteolytic enzyme that provides local modification of the ECM porosity. Multifunctional NPs such as these can be used to improve the biodistribution of drugs and genes directly injected into defined biological compartments such as tumors and fluid-filled organs such as the bladder and eye. Of additional interest is the capacity of SPM NPs to produce strong contrast in magnetic resonance (MR) imaging, providing another dimension for their use.
2c. Detection of Multiple Proteins from Complex MixturesEfforts to use modulated protein expression distribution as a method to identify emerging tumorigenesis are becoming reality. Early results suggest that detection of a panel of multiple proteins will be required for satisfactory predictive performance. Our lab is attempting to develop functionalized nanoparticles that agglomerate in the presence of specific proteins. By using nanoparticles with multiple unique characteristics, the complex spectral characteristics of an agglomerate can be 'unmixed' to assess the identity (and, perhaps, the relative concentration) of specific proteins. Such agglomerates would fail to form in the absence of the target proteins, generating undetectable agglomerates below the threshold of detection by flow cytometry, consistent with a negative test result. Such an approach leverages existing clinical instrumentation and may yield both a definitive signal indicating the expression of cancer-associated proteins and a spectral signature that offers additional information.
Engineering complement activation on polypropylene sulfide vaccine nanoparticles. Thomas, SN; van der Vlies, AJ; O'Neil, CP; Reddy, ST; Yu, SS; Giorgio, TD; Swartz, MA; Hubbell, JA, BIOMATERIALS, 32, 2194-2203 , (2011)
Kinetics of Molecular Recognition Mediated Nanoparticle Self-Assembly. Soman, C; Giorgio, T, NANO RESEARCH, 2, 78-84 , (2009)
Novel 7-mer peptide mediates nuclear targeting in MCF7 breast cancer cells. Lowery, AR; Finka, A; Dorset, DC; Hubbell, JA; Giorgio, TD, CANCER RESEARCH, 69, 354S-354S , (2009)
Quantitative Measurement of Multifunctional Quantum Dot Binding to Cellular Targets Using Flow Cytometry. Smith, RA; Giorgio, TD, CYTOMETRY PART A, 75A, 465-474 , (2009)
Sensitive and multiplexed detection of proteomic antigens via quantum dot aggregation. Soman, C; Giorgio, T, NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE, 5, 402-409 , (2009)
Surface functionalized nanoparticles for proximity-activated detection and imaging of breast cancer. Sewell, SL; Giorgio, TD, CANCER RESEARCH, 69, 348S-348S , (2009)
Synthesis and enzymatic cleavage of dual-ligand quantum dots. Sewell, SL; Giorgio, TD, MATERIALS SCIENCE & ENGINEERING C-BIOMIMETIC AND SUPRAMOLECULAR SYSTEMS, 29, 1428-1432 , (2009)
Proximity-activated nanoparticles: in vitro performance of specific structural modification by enzymatic cleavage. Smith, RA; Sewell, SL; Giorgio, TD, INTERNATIONAL JOURNAL OF NANOMEDICINE, 3, 95-103 , (2008)
Quantum dot self-assembly for protein detection with sub-picomolar sensitivity. Soman, CP; Giorgio, TD, LANGMUIR, 24, 4399-4404 , (2008)
Superparamagnetic nanoparticles as a powerful systems biology characterization tool in the physiological context. Salaklang, J; Steitz, B; Finka, A; O'Neil, CP; Moniatte, M; van der Vlies, AJ; Giorgio, TD; Hofmann, H; Hubbell, JA; Petri-Fink, A, ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 47, 7857-7860 , (2008)
Development of challenge-based educational modules in the biotechnology domain. Birol, G; McKenna, AF; Smith, HD; Giorgio, TD; Brophy, S, INTERNATIONAL JOURNAL OF ENGINEERING EDUCATION, 23, 171-183 , (2007)
Facile production of multivalent enzyme-nanoparticle conjugates. Kuhn, SJ; Finch, SK; Hallahan, DE; Giorgio, TD, JOURNAL OF MAGNETISM AND MAGNETIC MATERIALS, 311, 68-72 , (2007)
Characterization of superparamagnetic nanoparticle interactions with extracellular matrix in an in vitro system. Kuhn, SJ; Hallahan, DE; Giorgio, TD, ANNALS OF BIOMEDICAL ENGINEERING, 34, 51-58 , (2006)
Proteolytic surface functionalization enhances in vitro magnetic nanoparticle mobility through extracellular matrix. Kuhn, SJ; Finch, SK; Hallahan, DE; Giorgio, TD, NANO LETTERS, 6, 306-312 , (2006)
Convective flow increases lipoplex delivery rate to in vitro cellular monolayers. Harris, SS; Giorgio, TD, GENE THERAPY, 12, 512-520 , (2005)
The Quantum Dot Nanoconjugate Toolbox. Tomlinson, ID; Wright, DW; Giorgio, TD; Blakely, RD; Pennycook, SJ; Hercules, D; Bentzen, L; Smith, RA; McBride, J; Vergne, MJ; Rosenthal, SJ, PROGRESS IN BIOMEDICAL OPTICS AND IMAGING, 199, 5705 , (2005)
Cell-based screening: a high throughput flow cytometry platform for identification of cell-specific targeting molecules. Smith, RA; Giorgio, TD, COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 7, 141-151 , (2004)
Differential phage display for discovery of nuclear localization peptides: Application to mammary adenocarcinoma. Weiner, AA; Giorgio, TD, MOLECULAR THERAPY, 9, S11-S12 , (2004)
Quantitation and kinetics of CD51 surface receptor expression: Implications for targeted delivery. Smith, RA; Giorgio, TD, ANNALS OF BIOMEDICAL ENGINEERING, 32, 635-644 , (2004)
A model for the analysis of nonviral gene therapy. Banks, GA; Roselli, RJ; Chen, R; Giorgio, TD, GENE THERAPY, 10, 1766-1775 , (2003)
Hyperacute lung rejection in the pig-to-human model. III. Platelet receptor inhibitors synergistically modulate complement activation and lung injury.. Pfeiffer, S; Zorn, GL; Zhang, JP; Giorgio, TD; Robson, SC; Azimzadeh, AM; Pierson, RN, TRANSPLANTATION, 75, 953-959 , (2003)
Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Hallahan, D; Geng, L; Qu, SM; Scarfone, C; Giorgio, T; Donnelly, E; Gao, X; Clanton, J, CANCER CELL, 3, 63-74 , (2003)
RNA interference (RNAi): Understanding mechanisms and optimizing for practical applications. Wyatt, SK; Patton, JG; Giorgio, TD, MOLECULAR THERAPY, 7, S207-S208 , (2003)
Computer-based educational granule development within the VaNTH ERC. Roselli, RJ; Giorgio, TD; Eggers, D; Owen, N; Brophy, S; Brock, J; Harris, TR; Collins, JC, FASEB JOURNAL, 15, A748-A748 , (2001)
Effect of platelet inhibition on pulmonary xenograft survival. Zorn, GL; Schroeder, C; Giorgio, TD; Farley, SM; Azimzadeh, AM; Robson, SC; Pierson, RN, XENOTRANSPLANTATION, 8, 32-32 , (2001)
Radiation-mediated control of drug delivery. Hallahan, DE; Qu, SM; Geng, L; Cmelak, A; Chakravarthy, A; Martin, W; Scarfone, C; Giorgio, T, AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS, 24, 473-480 , (2001)
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