Alexis R. Abramson is an Associate Professor in Mechanical and Aerospace Engineering at Case Western Reserve University. Until recently, she was also a Senior Fellow at NorTech, a tech-based economic development organization, and Executive Director of the Nano-Network, a Northeast Ohio nanotechnology organization which co-organized three past Nanomedicine Summit conferences. Alexis has worked with various entities around Northeast Ohio, promoting innovation and technology commercialization, including a "Partnership for Innovation" program ongoing at CWRU. Dr. Abramson's research focuses on understanding and manipulating nanoscale energy transport in nanocomposites, nanostructures and biological materials for thermal management applications. She is the author of a number of publications in her research field.
     Dr. Abramson has also been involved in various engineering education outreach programs and has a dedicated interest in improving science and engineering education for all ages. Alexis obtained her Ph.D. in Mechanical Engineering from the University of California, Berkeley in 2002 where she was a National Science Foundation Fellow, and her B.S. and M.S. degrees in Mechanical Engineering from Tufts University in Medford, MA.

James Basilion completed his BA in biochemistry at the University of Pennsylvania in 1984 and entered the doctoral program at the Graduate School of Biomedical Sciences, University of Texas Health Science Center at Houston. Following his graduate studies Dr. Basilion took a post-doctoral fellowship at the National Institutes of Health (NICHD) where he began working collaboratively with scientists at the Massachusetts General Hospital (MGH). In 1999, after a few years as a Senior Scientists in a Biotech startup, Dr. Basilion joined the Faculty of Harvard Medical School and MGH- Center for Molecular Imaging Research as an Assistant Professor of Radiology. In September 2005 Dr. Basilion joined the faculties of Medicine and Engineering at Case Western Reserve University and directs the NFCR Center for Molecular Imaging at Case. Dr. Basilion was a founding member and officer of the Society for Molecular Imaging and holds editorships on three imaging or imaging related journals.
     His vision for the Society of Molecular Imaging is to promote its growth and development while keeping its meeting fun and informative to attend. Another goal is to further the attraction of “outsiders” from different disciplines and promote the use of Molecular Imaging in their research efforts.

Therapeutic Nanoparticles to Combat Brain Tumors

James P. Basilion^1,3, Yu Cheng², Joseph Meyers³, Ann-Marie Broome^1,3, and Clemens Burda² Case Western Reserve University ¹Department of Biomedical Engineering, ²Department of Chemistry, ³Department of Radiology, and the NFCR Center for Molecular Imaging at Case

Brain cancer is a life threatening disease characterized by low survival rates. The development of selectively targeted drugs for diagnosis and therapy is critical for improving the diagnosis and treatment of this aggressive type of cancer. Photodynamic therapy (PDT) is a localized treatment modality that is promising for brain tumor treatment. Improvements in survival were reported, however, the widespread use of PDT in brain tumor therapy has been partially restrained by non-targeted phototoxicity towards healthy tissue. Improving the tumor delivery and selectivity of PDT drugs will dramatically enhance the success of brain cancer therapy.
     Pc 4 is a highly promising PDT drug, approved for clinical trials, characterized by virtual non-toxicity in the dark, high phototoxicity (1O2 quantum yield of F? = 35%, when attached to the NP), well defined chemical structure and purity. Its long absorption (670 nm) and emission (680 nm, Ffl = 40%) wavelengths allow to operate this drug in the useful near infrared (NIR) spectral window that penetrates brain tissue most efficiently for diagnostic optical imaging and phototherapy using NIR light.
     Here we describe a novel nanoparticle delivery system that dramatically increases bioavailability of the agent to the tumor and has potential for enabling PDT for brain tumors.

Maciej Zborowski, is staff in the Department of Biomedical Engineering, Lerner Research Institute of Cleveland Clinic and the Associate Professor in the department of Molecular Medicine of the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University (CWRU) Cleveland Ohio. He received M.Sc. degree (Biophysics 1975) from Warsaw University and Ph.D degree (Biomedical Engineering 1985) from Polish Academy of Sciences, Warsaw, Poland. He directs Cell Separation Research Laboratory whose focus is research and development in the area of instrumentation for fast cell sorting, in particular, magnetic cell sorting. This requires application of fine magnetic particles (nanoparticles) for cell tagging and separation. The collaborators include Drs. Ernest Borden and Jarek Maciejewski in the Cleveland Clinic Taussig Cancer Center, Dr. Jeff Chalmers at Ohio State University, Columbus Ohio, and Dr. Peter Zimmerman at the Global Health and Diseases, CWRU.

Eben Alsberg is an Assistant Professor in the Departments of Biomedical Engineering and Orthopaedic Surgery at Case Western Reserve University. Dr. Alsberg is currently Director of the Alsberg Stem Cell and Engineered Novel Therapeutics (ASCENT) Laboratory. A primary focus of his laboratory is engineering functional biologic replacements to repair damaged or diseased tissues in the body. Complex signals that are implicated in tissue morphogenesis, repair, and homeostasis are used as a template for the development of innovative biomaterials for tissue regeneration. Through the precise temporal and spatial presentation of soluble bioactive factors, mechanical forces, and biomaterial physical and biochemical properties, microenvironments are created that regulate cell gene expression and new tissue formation. He has co-authored 40 peer reviewed papers and has recently been chosen as a 2008 Ellison Medical Foundation New Scholar on Aging and a recipient of the Crains Cleveland Business 2009 Forty Under 40 Award.

Guiding Cellular Behavior and Organization

Tissue engineering is an exciting field as it holds the promise of technologies permitting and promoting the regeneration of lost or damaged organ function. One approach to this goal is providing specific signals to cells in a controlled manner both spatially and over time in order to regulate their behavior. This talk will focus on two different research areas utilizing functionalized nanobiomaterials for tissue engineering. The first involves the development of nanofibrous scaffolds with controlled cell adhesive properties. Biomaterial nanostructure has previously been shown to influence cell behaviors such as alignment, migration, and growth. Here, nanofibrous scaffolds that allow for the study of the affects of biomaterial nanostructure and adhesivity independently and in combination on cell behavior will be presented. The second research area focuses on the utilization of passivated, cytocompatible magnetic nanoparticles to create ordered linear arrangements of cells. The ability to spatially pattern cells in defined configurations may ultimately accelerate the formation of tissue structures.

Ananth Annapragada is the Robert H. Graham Professor of Entrepreneurial Biomedical Informatics and Bioengineering, The University of Texas Health Sciences Center at Houston. Dr. Annapragada is a Chemical Engineer by training and worked in the Pharmaceutical Industry for over 10 years before returning to Academia. He directs the Laboratory for Computational Biology and Delivery Systems (LCBDS) at the University of Texas. LCBDS activities are all in the general area of Future Medical Technologies, based on nanotechnology platforms. Work in his lab has resulted in the formation of 3 startup companies to date: Marval Biosciences Inc., Cense Biosciences Inc. and InSilico Therapies Inc.

Nanoparticle Based Drug and Contrast Agent Delivery Systems

While technologies to improve the pharmacokinetics, organ distribution and toxicity of drugs have been developed and improved for decades, the translation of these technologies to the delivery of imaging contrast agents has been scarcely explored. In this presentation, the application of Stealth liposome technology to the delivery of imaging contrast agents for CT and MRI will be described. Two agents, NCTX and NMRX have been developed, optimizing their imaging signal strength, organ distribution and lesion localization. These agents facilitate single-scan imaging of the entire blood pool, as well as longitudinal tracking of the evolution of localization. This potentiates simultaneous diagnosis of multiple possible anomalies. Further, the tracking of therapeutic effects, and the prediction of therapeutic efficacy are enabled in specific applications.
     Specific examples of such applications that will be presented in this talk include total blood pool imaging, simultaneous imaging of left- and right-heart circulation, simultaneous pulmonary embolism detection and coronary angiography, tracking effects of clot-dissolving drugs (rTPA), the the prognostication of cancer chemotherapy efficacy via preliminary imaging, thus separating cancer patients into chemo-responsive and non-chemo-responsive groups, and the imaging of cerebral amyloidopathies.

Dr. Efstathios (Stathis) Karathanasis is an Assistant Professor of Biomedical Engineering and Radiology at Case Western Reserve University.
     He directs the Laboratory for Nanomedical Engineering (part of Case Center for Imaging Research). Specifically, his lab focuses on the development of imaging and therapeutic agents based on the integration of nanotechnology and engineering with imaging to enable personalized cancer therapies. Dr. Karathanasis is a coinventor on a nanoscale contrast agent for probing vascular integrity using x-ray-based imaging (a technology assigned to Marval BioSciences Inc., Houston, TX). He received his bachelor’s and doctoral degrees in Chemical Engineering from Aristotle University of Thessaloniki in Greece and University of Houston, respectively and completed a postdoctoral fellowship in Biomedical Engineering at Georgia Institute of Technology.

Assembly of Nanoworms from nanoparticles with controlled topology of surface ligands

Pubudu M. Peiris, Erik Schmidt, Michael Calabrese, Efstathios Karathanasis Case Center for Imaging Research, Department of Biomedical Engineering and Department of Radiology, Case Western Reserve University

Nanomedicine’s greatest advantage is the ability to combine more than one function by enabling the design of multi-component nanoparticles that target, image, and destroy tumors. Besides the multifunctionality, another equally important aspect is the engineerability of nanoparticles to control the geometrical and chemical properties during fabrication. By exploiting the engineerability of nanoparticles, we are able to define the chemical properties by controlling the topology of ligand expression on the surface of various types of nanoparticles (e.g. liposome, dendrimer, metal particles). Here, we will report on a class of such “Janus” particles consisting of iron oxide nanoparticles with two faces, one displaying only amines and the other only thiols. The two unique faces on the same particle serve as fittings to assemble the Janus particles into nanoworms in a controlled manner. The worm can consist of various members (e.g. different type and size of nanoparticles) whereas the inner-worm distance between members can be adjusted. The unique properties of such nanoworms for image-guided therapies and molecular imaging applications will be discussed.

Dr. Steinmetz’s major area of professional interest lies with the application of complex viral nanoparticle formulations for biomedicine and materials science. Dr. Steinmetz will start as an Assistant Professor in the Department of Biomedical Engineering at Case Western Reserve University, Cleveland, OH, USA, in the fall of 2010. As a post-doctoral fellow at The Scripps Research Institute, La Jolla, CA, USA, her efforts have focused on the development of viral nanoparticle formulations for cancer detection and treatment (2007-2010). During her dissertation work at the John Innes Centre, Norwich, UK, she created multiple 3D VNP multilayered thin film arrays for potential applications in sensors or nanoelectronics (2004-2007). Dr. Steinmetz is a 2009 recipient of the NIH/NIBIB Pathway to Independence Grant (K99/R00), a previous American Heart Association Post-doctoral Fellow, former Marie Curie EST Fellow, winner of the Bryan Harrison Prize (2006), and 2007 Biosciences Federation Science Communication Award winner. Her early training was at RWTH-Aachen University in Germany, where she received her Diploma (equivalent to Masters) with Honors in 2004.

Viral Nanoparticles (VNPs): Tools for Applications in Biomedicine

The use of nanomaterials has the potential to revolutionize materials science and medicine. Currently, a number of different nanoparticles are being investigated. Viral nanoparticles (VNPs) derived from plant viruses, such as the Cowpea mosaic virus and Potato virus X, can be regarded as naturally occurring nanomaterials. From a materials scientist’s point of view, VNPs are attractive building blocks for several reasons: the particles are monodisperse, can be produced with ease on large scale, are exceptionally stable, and biocompatible. VNPs are “programmable” units, which can be modified using genetic modification or chemical bioconjugation methods.
     Viral nanotechnology is a young and emerging discipline. VNPs are promising candidate materials for the development of “smart” devices for applications in medicine. VNPs are of tremendous interest for applications in tissue-specific imaging or targeted drug-delivery. Chemotherapy for cancer and vascular disease is generally not targeted, thus many undesired side effects occur. Targeting drugs specifically to sites of disease while avoiding healthy tissues, is expected to reduce toxic side effects, improve quality of life, and is an important goal in biomedicine. I will highlight examples that demonstrate the feasibility of targeting VNPs to sites of disease in vivo. VNPs can be interlinked with targeting ligands, imaging modalities, and therapeutic moieties. Such ‘smart’ multifunctional devices are expected to find applications in targeted chemotherapies.

Wiley Youngs is originally from northern New York State. He received a B.A. in Psychology from the State University of New York at Albany and returned to school to further pursue his undergraduate education in chemistry at SUNY Potsdam and Clarkson University. He received his Ph.D. in 1980 under the supervision of Melvyn Churchill at SUNY Buffalo. Following a postdoctoral fellowship with James Ibers at Northwestern University, he joined the faculty at Case Western Reserve University in 1983. In 1990, he moved to the University of Akron where he currently holds the rank of Distinguished Professor of Chemistry. Dr. Youngs’ research interests include N-heterocyclic carbenes, silver based antimicrobials, metal-based cancer drugs, and fuel cell membrane materials

Antimicrobial And Antitumor Properties Of Silver (I) Carbene Complexes Encapsulated In Nanoparticles

Wiley J. Youngs, Claire A. Tessier, Matthew Panzner, Nikki Robishaw, Amanda Knapp, Patrick Wagers, Michael Deblock, Center for Silver Therapeutics Research University of Akron; Carolyn L. Cannon, University of Texas Southwestern Medical Center; Mark Estes, University of Texas Medical Branch Galveston; Jeff Leid, University of Northern Arizona; Anirban Sen Gupta, Case Western Reserve University

Much of our research focuses on the development of silver-based antimicrobial agents, silver carbene complexes (SCCs), for use as a broad-spectrum therapy for patients with cystic fibrosis (CF). These patients experience respiratory decline due to chronic pulmonary infections with multiple pathogens including Pseudomonas aeruginosa. We have found that SCCs have antimicrobial activity against all CF pathogens tested to date, including multi-drug resistant species. Silver carbenes have broad spectrum activity against virtually all bacteria, including NIAID Category A and B bacteria Y. pestis, B. anthracis, B. mallei and B. pseudomallei and the Emerging Infectious Disease bacterium, methicillin-resistant S. aureus (MRSA). Three years ago we began to study the effect of SCCs on a wide variety of cancer cells. This research showed that SCCs are very effective against a variety of cancers including lung cancer. A major focus of our research is now on the encapsulation of SCCs into nanoparticles for prolonged delivery to the lungs and for targeted systemic delivery. Encapsulation of SCCs within biodegradable polymeric nanoparticles is designed to protect the silver complexes from chloride and argyrophilic proteins in the blood there by allowing for systemic delivery. Nanoparticles, including micelles, containing SCCs have been formed. Portions of our studies on the in vitro and in vivo antimicrobial and antitumor properties of SCC nanoparticles will be presented.
     This work was supported by the University of Akron through a Faculty Research Grant, University of Texas Southwestern Medical Center, Washington University School of Medicine, the National Institute of Allergies and Infectious Diseases (1 R01 A106785601) and the National Institute of General Medical Sciences (1 R01 GM86895-01)

Novel Technology Approaches to Circulating Tumor Cell Capture, Detection and Characterization

Evaluation of circulating tumor cells (CTC) allows assessment of disease status and therapeutic efficacy.  The available approaches for CTC detection largely depend on the antibody-mediated magnetic capture of the CTC using antibodies against the epithelial cell adhesion molecule (EpCAM), a feature which can be exploited in only a select few malignancies, and even in these cases, CTC capture is directly impacted by the variable expression. The current methods are thus limited by difficulties with sensitivity, specificity, efficiency, and high costs. We have developed a parylene-based portable microfilter device for size-based CTC capture. Compared with the FDA-approved CellSearch(r) platform, the microfilter was superior in CTC capture efficiency for cancer patient blood samples. Our platform incorporates a number of highly useful functionalities, both 'on-chip' (immunofluorescence, FISH, and DNA/RNA isolation) and 'off-chip' (array CGH). We have also embarked on developing a next-generation microfilter which has a capability to capture live CTC. In summary, this portable device will be clinically relevant for rapid processing at point of care, and useful in research through post-capture molecular analysis of the CTC, thus essentially serving as a "liquid" biopsy. We believe the technology has the potential to revolutionize the management and treatment of cancer patients.

Richard J. Cote, MD is Chair of the Department of Pathology at the University of Miami Miller School of Medicine and the University of Miami Health System, and chief of pathology for Jackson Memorial Hospital. Dr. Cote, a nationally recognized expert on the cellular and molecular markers of tumor progression in cancer patients, will also start and direct the University of Miami Biomedical Nanoscience Institute.
     A major research area for Cote has been the molecular biology of prostate and bladder cancer. His lab has identified the pathways by which cells become malignant, and the mechanisms by which the tumors progress.  Cote has led three of the largest clinical trials in breast, lung and bladder cancer, which were based on discoveries from his research that identified molecules and pathways important in assessing treatment response.
     A long standing area of focus has been to detect the earliest evidence of tumor spread into blood, bone marrow and lymph nodes in patients with no other evidence of metastatic disease from breast, lung and prostate cancer.      Cote is the recipient of over $35 million in peer reviewed grant support, and holds numerous patents for cancer related and nanoscale technologies. He is the author of over 300 publications, and is the editor and co-author of the standard textbooks “Immuno Microscopy: A Diagnostic Tool for the Surgical Pathologist” (now in its third edition), and “Modern Surgical Pathology,” the second edition of which will be out later this year. He also serves as a member and advisor to a large number of national and international study groups, cancer programs and societies, including the National Cancer Institute. He is the founder of several technology-based companies, including Impath, Inc. and Clarient. He is listed in “Best Doctors in America” and “America’s Top Doctors” and is a Fellow of the Royal College of Pathology.

Dr. Fleisher is Chairman of the Department of Clinical Laboratories and Chief of Clinical Chemistry at the Memorial Sloan-Kettering Cancer Center in New York City.  He is internationally recognized as an expert in the discovery and use of tumor markers and biomarkers for detecting and monitoring cancer.  Dr. Fleisher has over 125 publications, including books and book chapters on the efficacy of tumor markers in cancer detection.  His contributions to tumor marker and biomarker discovery involve development and validation of tests for colon, breast, prostate, ovarian and brain cancers.  Dr. Fleisher has received numerous awards for contributions to Cancer Research Diagnostics. He holds four U.S. patents for laboratory devices.  Dr. Fleisher received his Doctorate degree, with honors, from New York University.  His current research focuses on biomarker assay development and validation and the use of biomarkers for new targeted preclinical and clinical drug development.

Advances in Circulating Tumor Cell Analysis: Analytical Validation Must Precede Clinical Application

Martin Fleisher, PhD, FACB

Detecting Circulating Tumor Cells (CTC) in peripheral blood of patients with cancer has become a clinically relevant and important prognostic biomarker and has been shown to be predictive in monitoring patients post-therapy. Currently, one analytical method, the Veridex CellTrack Analyzer, is FDA approved for use in monitoring therapeutic response in patients with breast, prostate and colon cancers. The CellTrack enrichment technique requires expression of EpCAM by CTCs and the number of CTCs are correlated to therapeutic response. The Biomarker Discovery Laboratory (BDL) at MSKCC focuses on the analytical validation of new enrichment techniques and on the contribution of mutations and translocations in androgen receptor-dependent growth of prostate cancer. The BDL has validated assay procedures that permit detection of picogram concentrations of RNA that can be used to define molecular profiles of CTCs isolated and collected from patients with prostate cancer. The successful clinical application of these emerging CTC technologies and the genomic interrogation of cancer cells are the basis for further studies into the biology of prostate neoplasia. Once these new biomarker assays have been rigorous validated to Clinical Laboratory standards, they will represent an important prognostic tool in the clinical management of patients with prostate cancer.

Jeffrey Chalmer's research is in the area of bioengineering. He has a current interest/ projects in the broad areas of cell culture, ranging from the study of human stem and cancer cells to industrially relevant cells. He also has interest in the emerging area of functional genomics, especially as it is related to cell culture, cell separation, and cancer cells.
     One specific project involves the ability to identify and separate cells based on specific immunological markers. In collaboration with a colleague at the Cleveland Clinic Foundation, they have developed three new, patented immunomagnetic instruments. One of these instruments is an analytical device, while the other two are separation instruments. All three of these instruments have a large number of applications as indicated by the research support that includes the National Cancer Institute, the National Science Foundation, the Whitaker Foundation, and a private corporation. Some of these applications include: human stem cell separation for bone marrow transplants, isolation/separation of rare cancer cells circulating in human blood, and identification and separation of genetically engineered cells with specific phenotypes. Besides studying the engineering principles of this separation approach, exciting fundamental and applied biological questions are being addressed with respect to these isolated cells using the latest molecular techniques.
     Another research area involves the development of better fundamental understanding and scale-up criteria for bioprocesses using animal cells. While large-scale animal cell culture has become quite common, a number of important questions/issues remain unresolved. For example, what is the optimum hydrodynamic environment for a suspended or anchorage- dependent cell? What is the mechanism of action, from a molecular point of view, of surface active agents in cell culture medium? Finally, his research group is exploring collaborations with systems research faculty to develop approaches to understand the great wealth of genetic information which is rapidly becoming available. This research will have specific applications with respect to the cancer cell separation projects as well as more general interest.

Magnetic enrichment of CTCs by immunomagnetic separation of normal white blood cells

In collaboration with Dr. Zborowski at the Cleveland Clinic, we have developed flow-through, high volume magnetic sorters for therapeutic and diagnostic applications. Currently, the method is applied to separation of rare circulating tumor cells (CTCs) from consenting patients diagnosed with metastatic cancers (head and neck, and breast) in an effort to develop a better tool for treatment prognosis at the OSU Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute.

Dr. Lee is the Helen C. Kurtz Professor of Chemical and Biomolecular Engineering at The Ohio State University. He serves as the Director of NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymer Biomedical Devices, and Ohio Center for Multifunctional Polymer Nanomaterials and Devices at OSU. He received a BS degree from National Taiwan University in 1972, and a Ph.D. degree from University of Minnesota in 1979. His research interest includes nanotechnology, BioMEMS/NEMS and drug delivery. He has 220 journal publications, 25 patents and invention disclosures, and 10 book chapters. Dr. Lee received 13 Best Paper Awards in technical conferences. He is a Fellow of American Institute for Medical and Biological Engineering, and received the 2008 Malcolm E. Pruitt Award from Council of Chemical Research, 2008 Engineering/Technology Award and 2010 International Award from the Society of Plastic Engineers.

Immuno-targeted Lipoplex Nanoparticles for Oligonucleotide Delivery

Both chemical and engineering approaches were applied to design, synthesize and optimize oligonucleotides (antisense ODN, siRNA and microRNA) loaded lipoplex nanoparticles (LNPs). Their structure was characterized by various techniques including cryoTEM and their performance was tested both in vitro and in vivo using liver cancer and leukemia as two clinical models. A series of new cationic lipids were synthesized and tested as potent transfection agents. They demonstrated high liver localization and hepatocyte cell uptake as well as gene silencing in liver cancer studies using both siRNA and microRNA. Antibody(Ab)-targeted immuno-LNPs (ILNPs) can further enhance specific gene silencing and protein down-regulation by reducing TLR-driven activation and co-stimulation. This is demonstrated by delivering an antisense ODN against human Bcl-2 for leukemia treatment. Our results also showed that dual targeted ILNPs have enhanced selectivity, binding efficiencies and faster internalization than the individual ILNPs or the simple mixture of individual ILNPs. To achieve therapeutic, imaging and diagnostic functions, multi-component nanoparticles have drawn a great deal of interest in recent years. The conventional bulk mixing methods, however, cannot produce multi-component LNPs with uniform structure and composition. We have developed microfluidics and electrospray based new synthesis method capable of producing multifunctional dual-Ab ILNPs with newly developed lipids. This approach has great potential for future cancer treatment, particularly personalized nanomedicine.

Anand Ramamurthi, PhD is an Associate Staff in the Department of Biomedical Engineering at the Cleveland Clinic. He received a BE (Hons.) degree in Chemical Engineering from Bangalore University, India in 1994, and his MS and PhD, also in Chemical Engineering, from Oklahoma State University, Stillwater, OK in 1996 and 1999 respectively. He was subsequently an American Heart Association postdoctoral fellow at the Department of Biomedical Engineering at the Lerner Research Institute of the Cleveland Clinic (1999-2001), where he worked on designing biomaterials for aortic valve tissue engineering. In 2003, he joined the faculty of the Department of Bioengineering at Clemson University and the Medical University of South Carolina, Charleston, SC and was a tenured Associate Professor at the time of his departure from the institution in 2010. Dr. Ramamurthi directs a research program the focuses on biomimetic regenerative repair of extracellular matrix structures, specifically in cardiovascular tissues. He is interested in developing in situ treatments for abdominal aortic aneurysms (AAAs) that lead to their viable repair and regression. His efforts are specifically directed at the design and integration of innovative tools (e.g., growth factor cocktails, biomaterial scaffolds with aligned topography, nanomaterials, cell types, dynamic culture protocols) to (a) up-regulate elastin precursor synthesis, (b) recruit and replicate the biocomplexity of assembling these precursors into ultrastructural and functional mimics of native elastic matrix super-structures (e.g., fibers, sheets), and (c) stabilize the matrices against physiologic or pathologic breakdown. Dr. Ramamurthi has more than 30 peer reviewed publications and numerous abstracts and proceedings to his credit.

Dr. Zheng-Rong Lu is M. Frank and Margaret Domiter Rudy Professor of Biomedical Engineering at the Department of Biomedical Engineering, Case School of Engineering, Case Western Reserve University. In 2002, Dr. Lu was appointed to Assistant Professor in the Department of Pharmaceutics and Pharmaceutical Chemistry at the University of Utah. Subsequently, Dr. Lu was promoted to a tenured Associate Professor in 2006. Dr. Lu’s research efforts involve molecular imaging, image-guided photodynamic therapy, in vivo imaging of dose forms, polymeric drug delivery systems and multifunctional delivery systems for nucleic acid. He has over 100 peer-reviewed scientific publications, five book chapters and 70 abstracts and four US patents. He is a Principal Investigator of major grants from the NIH. Dr. Lu serves on the scientific advisory board of Pharmaceutical Research, Molecular Pharmaceutics and Journal of Molecular Imaging & Dynamics. Currently, Dr. Lu serves as a member of the NIH Clinical Molecular Imaging and Probe Development Study Section.

Zheng-Rong Lu Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio

Tumor microenvironment plays a critical role in cancer survival, proliferation and metastasis. Molecular imaging of biomarkers in tumor microenvironment provides accurate earlier detection and diagnosis of malignant tumors and non-invasive evaluation of anticancer therapeutics efficacy. We have designed and developed polydisulfide-based biodegradable macromolecular MRI contrast agents for evaluating tumor angiogenesis and targeted nanoglobular MRI contrast agents for detecting a cancer-related biomarker expressed in the extracellular matrix of malignant tumors. The biodegradable macromolecular contrast agents are effective for characterizing tumor angiogenesis and non-invasive evaluation of tumor response to cancer therapies in DCE-MRI. The targeted contrast agents specifically bind to the biomarker in tumor extracellular matrix, resulting in strong and prolonged contrast enhancement in the tumor tissue, not in normal tissues. The novel macromolecular MRI contrast agents have shown a potential for accurate characterization of tumor angiogenesis, timely evaluation of anticancer therapeutic efficacy and specific cancer molecular imaging with MRI.

Dr. Periannan Kuppusamy is a Professor in the Department of Internal Medicine, Ohio State University. He has developed a variety of in vivo EPR spectroscopic and imaging techniques for noninvasive measurements of free radicals and oxygen in biological systems. His major research focus is stem-cell therapy for myocardial infarction, novel therapeutics, and technology development for EPR-based oximetry for clinical applications. He has published over 300 manuscripts and several grants from NIH for the development of clinical oximetry and cardiovascular research. He received Doctorate of Medicine (honoris causa) in 2008 from the University of Pecs (Pecs, Hungary) for his cardiovascular research

Novel sensors and opportunities for EPR-based clinical oximetry

Oxygen is a critical determinant in the prediction of treatment outcome of several disease including surgical interventions, cancer therapy, tissue graft, and cell therapy. There is a great need for methods capable of reliable noninvasive measurement and monitoring of oxygen concentration in tissues. Although several methods are utilized to measure oxygen concentration, a suitable technique for noninvasive and repeated measurements of oxygen in the same tissue or cells on a temporal scale is warranted. Electron paramagnetic resonance (EPR) oximetry enables reliable and accurate measurements of concentrations of molecular oxygen. EPR oximetry can measure directly and at the actual site of interest. The ability of EPR oximetry to make repeated measurements from localized sites provides a very important capability that can enable critical aspects of a number of biomedical applications. We have developed innovative approaches using oxygen-sensing nano/microcrystalline probes to perform noninvasive oximetry/imaging in a variety of applications including myocardial ischemia/reperfusion injury, cellular cardiomyoplasty (cell therapy), tumor angiogenesis, cancer therapy, and wound healing. Current developments in in vivo EPR methodologies enable a number of potential applications that could be very significant additions to clinical medicine. The current developments of oximetry probes and designs for clinical oximetry will be presented.

Neal J. Meropol, MD, is Chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland, Ohio. He is also Associate Director for Clinical Research of the Case Comprehensive Cancer Center. A graduate of Vanderbilt Medical School, he completed his Hematology and Medical Oncology Fellowship at the University of Pennsylvania and his Internal Medicine Residency at Case Western Reserve University. Dr. Meropol’s national roles currently include Chair of the Developmental Therapeutics Committee and member of the Gastrointestinal Core Committee of the Eastern Cooperative Oncology Group. He is also Chair of the National Cancer Institute GI Steering Committee Colon Cancer Task Force. He has a variety of positions within the American Society of Clinical Oncology, including Chair of the Cancer Research Committee, Chair of the Comparative Effectiveness Task Force, and member of the Cost of Care Task Force. Dr. Meropol’s research includes therapeutic clinical trials, biomarker development, patient decision making, and comparative effectiveness

Dr. Uday B. Kompella is a Professor of Pharmaceutical Sciences and Ophthalmology at University of Colorado Anschutz Medical Campus. His research interests include design of nanoparticle technologies for drug delivery, gene delivery, and imaging. Dr. Kompella serves as an editor for the journal, Pharmaceutical Research, with a focus on articles related to nanotechnology.

Nanosystems for retinal drug and gene delivery

Delivery of therapeutic agents to the retina in the back of the eye is a challenge due to its anatomic location and the presence of multiple biological barriers. Nanotechnology has the potential to offer some unique solutions to overcome these barriers. A key focus of our research is to enhance retinal drug and gene delivery using nanosystems. We have successfully employed functionalized nanoparticles and novel dendritic polyguanidilyated translocators (DPTs) to enhance drug delivery to the back of the eye. Functionalized nanoparticles are superior to conventional nanoparticles in targeting various retinal cell layers including retinal pigment epithelial cells, photoreceptors, and endothelial cells. Our novel dendrimers, in addition to enhancing cell entry, allow enhanced drug solubility and tissue retention. This talk will present preclinical examples of various nanosystems intended for treating choroidal neovascularization, retinoblastoma, and infections of the eye.

After receiving his Ph.D. from U of Minnesota in 1987 and postdoctoral training at NIH, he joined Purdue University in 1990, tenured in 1993, became a full Professor in 1997, and was honored as Purdue Faculty Scholar in 1998. He constructed phi29 DNA packaging motor (PNAS, 1986), discovered phi29 motor pRNA (Science, 1987), assembled infectious viruses of phi29 using the DNA packaging motor he constructed, discovered pRNA hexamer (Mol Cell, 1998), pioneered RNA nanotechnology (JNN, 2003; Nano Lett., 2004, 2005) using phi29 pRNA for siRNA or drug delivery to specific cells, built a dual viewing system that can detect single-fluorophores (EMBO J, 2007; RNA, 2007), incorporated the phi29 motor channel into a lipid membrane (Nature Nanotechnology,2009) for single molecule sensing, and developed a new system with the potential for high throughput dsDNA sequencing. He received the Pfizer Distinguished Faculty Award in 1995; the Purdue Faculty Scholar award in 1998; the Purdue Seed Award in 2004, 2005, and 2007; the Lions Club Cancer Research Award in 2006; COV Distinguished Alumni of the University of Minnesota in 2009, and Distinguished Research Award in 2010. He is an editor or board member of four nanotech journals. His work has been reported hundreds of times over the radio, TV (such as ABC, NBC, and WLFI), and featured in NIH, NSF, MSNBC, and ScienceNow. He was a member of two prominent national nanotech initiatives sponsored by NIST, NIH, and NSF and the National Council of Nanotechnology; panelist of DOD Air Force, Army, and Navy; joined the 2003 medical assessment workshop; a member of the Beckman Foundation Research Initiatives in 2001 and 2009; and member of the review panel (site-visit) of National Cancer Institute Intramural Research Program in 2010.

Bacterial Virus Phi29 DNA Packaging nanomotor for single molecule sensing and specific drug delivery using protein and RNA nanotechnology

Peixuan Guo, Director of one NIH Nanomedicine Development Center with headquarter at University of Cincinnati, Cincinnati, OH

Living systems contain a wide variety of nanomachines that could serve as modules, tool boxes, or building blocks in nanotechnology.  DsDNA viruses transport the viral genome into a preformed protein shell with the aid of a nanomotor. The long term interest of this lab is the construction and study of phi29 DNA packaging motor that is geared by a six-RNA (pRNA) ring and uses ATP as energy. A mimetic DNA-packaging motor has been constructed and remains one of the strongest biomotors constructed in vitro. The 3D structures of the pRNA have been probed by photoaffinity crosslinking, chemical modification interference, compensatory modification, cryo-AFM, and 3D computer modeling. Current active projects in the lab include 1) Construction of single molecule dual fluorescent imaging instrument to measure the distance and count the stoichiometry of motor components. 2) The ingenious design of phi29 nanomotor with an elaborate central channel has inspired its application for single molecule sensing and single channel dsDNA sequencing using the channel of the nanomotors. 3) The use of motor pRNA as a building block for bottom-up assembly in nanotechnology for targeted delivery of siRNA and drugs. The polyvalent pRNA based nanoparticle can deliver up to six kinds of therapeutics to specific cancer and viral infected cells. Incubation of the RNA nanoparticles containing a receptor-binding aptamer or ligand resulted in cell binding and entry of chimeric pRNA/siRNA, pRNA/ribozyme, or drugs into cells, subsequently inducing programmed cell death. The delivery and therapeutic efficiency was confirmed in animal trials. Using such protein-free nanoparticles as therapeutic reagents would allow for long-term administration to avoid immune responses due to repeated treatment of chronic diseases.

Yogen Saunthararajah is Associate Staff in the Department of Hematologic Oncology and Blood Disorders at the Taussig Cancer Institute. Dr Saunthararajah is a graduate of the University of Wales College of Medicine and completed his training in Hematology and Oncology at the National Institutes of Health in Bethesda, Maryland. Dr Saunthararajah’s group is supported by the National Institutes of Health and the Department of Defense in their efforts to develop cancer and blood disease treatment that is not toxic to normal stem cells, and which does not depend on apoptosis genes which are frequently mutated in cancer cells.

Using nanomaterials to facilitate non-cytotoxic, p53 independent oncotherapy

The proliferative advantage of cancer cells can be acquired by aberrant repression of late differentiation genes that terminate proliferation. Although mutation or translocation of master regulators of differentiation may be upstream triggers for this aberrant repression, chromatin modifying enzymes mediate the effect. Therefore, depleting the chromatin modifying enzyme DNA-methyl-transferase 1 (DNMT1) from cancer cells, using low concentrations of the cytosine analogue decitabine that do not cause apoptosis, terminates proliferation through resumption of differentiation. Important advantages of this treatment approach are broad activity unrestricted by cancer sub-type or genetics, non-dependence on TP53 or other apoptosis genes that are frequently deleted or mutated in cancer cells, and lack of toxicity to normal stem cells. The latter allows frequent drug administration to sustain the therapeutic effect. This constitutes an exciting approach that is mechanistically distinct from conventional apoptosis-based therapy. However, cancer cell resistance, involving stratagems to prevent the DNMT1 depleting effect of decitabine, occurs. We describe use of nanomaterials to overcome cancer cell resistance to the pharmacologic effects of decitabine, towards a novel paradigm of non-cytotoxic epigenetic-differentiation therapy for cancer.

Deryl Troyer, professor of anatomy and physiology at Kansas State University, has spent his life as a research scientist and teacher focusing on developmental defects, gene mapping, stem cell biotechnology and cancer.
     Troyer has discovered, along with colleagues at K-State, a novel and potentially inexhaustible source of stem cells isolated from the matrix of umbilical cords. These cells have a remarkable propensity to traffic to areas of pathology including cancer. His laboratory has shown that they can be used for cell-directed gene therapy of cancer, and is currently working on ways they can deliver other therapies such as small anticancer molecules in nanoparticles, magnetic nanoparticles for hyperthermia, or in situ photodynamic therapy. His laboratory also is investigating the role of cancer stem cells in tumor growth and invasiveness.
     Troyer received his Doctor of Veterinary Medicine in 1972 and a doctoral degree in anatomy and physiology in 1985, both from K-State. He has been teaching in the department of anatomy and physiology in the College of Veterinary Medicine at K-State since 1986. Troyer also was an assistant professor in the College of Veterinary Medicine at the University of Illinois, Urbana, and was a visiting researcher in molecular genetics at Ray White's laboratory at the Howard Hughes Medical Institute in Salt Lake City, Utah, in 1988.
     Troyer is a member of the American Association for Cancer Research, American International Society for Stem Cell Research, Association for the Advancement of Science, American Genetic Association, International Society for Animal Genetics and the Kansas Academy of Science. He also is involved in the American and World associations of Veterinary Anatomists and the American and Kansas Veterinary Medical associations.
     His honorary memberships include Gamma Sigma Delta, Phi Kappa Phi, Phi Zeta, Alpha Zeta and Sigma Xi. Troyer also received the Pfizer Award for Research Excellence in 1996, the IVX teaching award in 2005, and the Teva teaching award in 2009. He is a laureate of the Ziestszchmann Prize for experimental veterinary embryology, and he is a founding core scientist in the Midwest Center for Comparative Stem Cell Biology.

Stem cells as ‘stealth’ delivery vehicles for anti-cancer therapeutics

Deryl Troyer¹, Viktor Chikan² and Stefan Bossmann², Departments of Anatomy and Physiology¹ and Chemistry², Kansas State University, Manhattan, KS 66506

There is now compelling evidence that a variety of mulitpotent stem cells can preferentially migrate to tumors to deliver anticancer molecules locally. Examples of such cells include bone marrow mesenchymal stem cells, neural stem cells, adipose derived stem cells and umbilical cord mesenchymal cells derived from Wharton’s jelly. The latter cells have also been demonstrated to have significant intrinsic anti-tumor effects as naïve cells against rat mammary carcinoma, mouse pancreatic cancer and mouse non-small cell lung cancer in vivo. These cells are attractive for cytotherapy because they do not themselves form tumors, are immunologically well tolerated, can be isolated non-invasively in large numbers. We have engineered these cells to secrete cytokines such as beta interferon to attenuate human metastatic breast cancer in mice. We are also testing these and other cells as delivery vehicles for anti-cancer nanotherapy. Here we will present data indicating that neural stem cells pre-loaded with core/shell Fe/Fe3O4 magnetic nanoparticles can attenuate mouse melanoma tumors after IV administration and exposure to an A/C alternating magnetic field.

Neal J. Meropol, MD, is Chief of the Division of Hematology and Oncology at University Hospitals Case Medical Center and Case Western Reserve University in Cleveland, Ohio. He is also Associate Director for Clinical Research of the Case Comprehensive Cancer Center. A graduate of Vanderbilt Medical School, he completed his Hematology and Medical Oncology Fellowship at the University of Pennsylvania and his Internal Medicine Residency at Case Western Reserve University. Dr. Meropol’s national roles currently include Chair of the Developmental Therapeutics Committee and member of the Gastrointestinal Core Committee of the Eastern Cooperative Oncology Group. He is also Chair of the National Cancer Institute GI Steering Committee Colon Cancer Task Force. He has a variety of positions within the American Society of Clinical Oncology, including Chair of the Cancer Research Committee, Chair of the Comparative Effectiveness Task Force, and member of the Cost of Care Task Force. Dr. Meropol’s research includes therapeutic clinical trials, biomarker development, patient decision making, and comparative effectiveness.

Mike Bunker joined Early Stage Partners (ESP) as Managing Director in 2008 to lead investments in the life science sector. With prior M&A roles for strategic acquirers, Mike provides young companies and entrepreneurs the framework for a successful exit through hands on investing. He currently serves on the board of several ESP portfolio companies, including Juventas Therapeutics (regenerative medicine), Cardiox (stroke diagnostic), Great Lakes Pharmaceuticals (Catheter Lock anti-infective) and HistoSonics (BPH treatment device). Mike also sits on the Commercialization Advisory Board for the Global Cardiovascular Innovation Center helping make grant decisions to Ohio’s leading early-stage medical technologies.
     Prior to joining ESP, Mike held roles in sales management and corporate acquisitions for C.R. Bard (NYSE: BCR). As Director of Corporate Development, he developed the business development process leading to the company’s most acquisitive time in their history. Later, Mike managed a field sales force and negotiated hospital contracts for a division of CR Bard.
     Mike joined Medtronic (NYSE: MDT) in 1998 where he first led a $750 global product launch in cardiac rhythm management and then served in Medtronic’s corporate development group responsible for all M&A activity. His experience there generated many successful minority investments, divestitures and acquisitions in support of multiple business units.
     Mike is a graduate of Miami University in Ohio and the Kellogg Graduate School of Management at Northwestern University.

Prof. Burda received his chemistry education in Switzerland and graduated as a doctor of philosophy and science with honors in 1997 from the University of Basel. Since 2001 he is appointed as a faculty in Physical Chemistry specializing on Nanoscience and Nanotechnology. His interests revolve around optically active or activatable nanomaterials for energy conversion, environmental studies, and health applications. Dr. Clemens Burda is the Director of the Center for Chemical Dynamics and Nanomaterials Research in the Chemistry Department, Case Western Reserve University. This applies in areas such as photobiology and biomedicine, including bioimaging, therapy and tissue targeting for drug delivery. Dr. Burda is a reviewer for top-ranked nanoscience and chemistry journals, an editorial member for the International Journal of Nanotechnology, and an organizer of national SPIE and ACS meetings. He is also the co-founder of Cleveland Nanocrystal Inc. Dr. Burda co-authored a review on "The Chemistry and Properties of Nanocrystals of Different Shapes", which is one of the most cited publications during the past 5 years.

Gold nanoparticles for photodynamic therapy and drug delivery

Yu Cheng¹, Joseph Meyers², James P. Basilion^2,3, Ann-Marie Broome^2,3, Malcolm E. Kenney^{1, and Clemens Burda14 Case Western Reserve University 1Department of Chemistry, 2Department of Biomedical Engineering, 3Department of Radiology, 4Materials Science and Engineering}

This talk will highlight the importance of choosing the interaction between the gold nanoparticle and drug molecules that are supposed to be transported to the diseased site. Gold nanoparticle conjugates with phthalocyanine drugs attached as a function of the bond to the nanoparticles have been synthesized and tested for delivery efficiency and photodynamic therapy (PDT) efficacy in HeLa cancer cells. It could be shown that the delivery and PDT outcome are strongly affected by the bond that links the drug to the nanoparticle surface. Labile amino adsorption to the gold nanoparticle surface allows for efficient drug release into the cancer cells by membrane diffusion within four hours and efficient PDT outcome. The subcellular localization of the drug delivered by gold nanoparticles is similar to the free drug. Whereas a covalent thiol bond to the gold nanoparticle leads to the delivery of the drug into cell vesicles, and no significant PDT effect is observed.

Mr. Monica has considerable litigation experience in defending national and international products liability claims for Fortune 500 companies. He is a nationally recognized authority on nanotechnology environmental, health, and safety; insurance; consumer product; product liability issues. Mr. Monica wrote the full length legal treatise Nanotechnology Law, which is updated and published yearly by West/Thomson/Reuters. Mr. Monica has participated in the development of voluntary international nomenclature and EHS standard for the nanotechnology industry. Additionally, he has successfully represented numerous clients in a variety of general commercial litigation matters in state and federal courts. Mr. Monica was named as one of the top ten experts in environmental, health and safety issues related to engineered nanoscale materials by Nanotechnology Law & Business peer-reviewed journal in April 2009.