2008 Nanobiotechnology Seminar Series

Seminar & Discussion 4:30 - 5:30 pm
Reception 5:30 - 6:00 pm

January 15, 2008 Clark Auditorium

Shuming Nie, Ph.D. 
Wallace H. Coulter Distinguished Chair Professor
Biomedical Engineering
Georgia Tech &

Nanotechnology for Cancer Molecular Imaging and Targeted Therapy: from Quantum Dots to SERS 

Nanotechnology is an interdisciplinary area of research in science, engineering, and medicine with broad applications for molecular imaging, molecular diagnosis, and targeted therapy. The basic rationale is that nanometer-sized particles such as semiconductor quantum dots (QDs) have novel optical, electronic, magnetic, and structural properties that are not available from either individual molecules or bulk solids. When linked with biotargeting or biorecognition ligands such as monoclonal antibodies, peptides, or small molecules, these nanoparticles can be used to target molecular biomarkers as well as diseased organs with high affinity and specificity. In the “mesoscopic” size range of 10-100 nm (diameter), quantum dots and polymeric nanoparticles also have more surface areas and functional groups that can be linked to multiple diagnostic (e.g., optical, radioisotopic, or magnetic) and therapeutic (e.g., anticancer) agents. Recent developments include a new class of size-minimized quantum dots for molecular and cellular imaging at the single-particle level, and a new class of nontoxic nanoparticles for in-vivo tumor targeting and spectroscopic detection based on the use of pegylated colloidal gold and surface-enhanced Raman scattering (SERS).

February 19, 2008 Clark Auditorium

Xiaoyuan (Shawn) Chen, Ph.D. 
Assistant Prof., Dept. of Radiology, MIPS

What's Next in Nanobio 

The convergence of nanotechnology and biotechnology has created and will continue to produce many excitements in the study of single molecules, biomimetics and biological nanostructure, electronic-biology interface, nanodevices for early detection of diseases, tissue engineering, molecular imaging and therapy. Despite the dazzling potential of nanobiotechnology to improve health care, there are also enormous technical hurdles for the translation of the scientific findings in the bench to the bedside. This talk will focus on the discussion of the current status and future perspective of nanotechnology in molecular imaging and therapy. 

March 18, 2008 Clark Auditorium

Xiaogang Peng, PhD 
Scharlau Professor of Chemistry
Dept of Chem & Biochem
Univ of Arkansas

Non-Cadmium Quantum Dots by Bandgap-Composition Engineering for Bio-Medical Imagining 

Semiconductor nanocrystals (quantum dots) are considered as the next generation labeling reagents for bio-medical imaging and sensing. Unfortunately, the current workhorse of quantum dots, CdSe and related materials, are so intrinsic toxic that they don’t have a real-life future. The nanocrystals without heavy metal ions, however, are with poor efficiency and poor stability. In addition, both CdSe based nanocrystals and the nanocrystals without non-heavy metal possess poor biocompatibility, including non-specific bonding, surface conjugation, and physiological permeability in biological tissue. This talk will discuss approaches to meet these challenges.

April 15, 2008 Clark Auditorium

Thomas J. Meade, PhD 
Eileen M. Foell Prof.,
Dept. of Chemistry
Northwestern Univ.

The Coordination Chemistry of Molecular Probes: Its all about the Background 

Fundamental biological and clinical questions have driven technological advances in a number of diagnostic techniques. From ex-vivo DNA chip-analysis, to in vivo molecular imaging, the last decade has seen significant advances and it is clear that this trend will continue. In vivo molecular imaging has demonstrated the ability to profoundly change our understanding of these events. One technique that has been a powerful tool in both experimental and clinical settings is magnetic resonance imaging (MRI). MRI offers a non-invasive means to map structure and function by sampling the amount, flow or environment of water protons in vivo. Such intrinsic contrast can be augmented by the use of paramagnetic contrast agents in both clinical and experimental settings. It is non-invasive and yields a true volume rendering of the subject with near cellular resolution (~10 microns). Currently, the direct observation of ongoing developmental events in living embryos and the descendants of individual precursors in an intact embryo are labelled by microinjection of a stable, nontoxic, membrane impermeable MRI lineage tracers. Since a complete time-series of high-resolution three-dimensional MR images can be analyzed forward or backward in time, it is possible to reconstruct the cell divisions and cell movements responsible for any particular descendant(s). Unlike previous methods, where labelled cells are identified at the termination of the experiment, this technique allows the entire kinship relationships of a clone to be determined. In order to realize the potential of this technique a high efficient means of delivering charged MR contrast agents must be developed. In order to understand signal transduction mechanisms of gene expression in whole animals we have developed a library of molecular MR probes that are biochemically activated in-vivo. The lanthanide chelates modulate fast water exchange with the paramagnetic center, yielding distinct "strong" and "weak" relaxivity states. The modulation is triggered by two types of biological events: i. enzymatic processing of the contrast agent and, ii. the reversible binding of an intracellular messengers (e.g., Ca2+, Zn2+).

May 20, 2008 Clark Auditorium

Otto Zhou, PhD
Lyles Jones Distinguished Professor of Physics and Materials Sciences

Carbon Nanotube X-Ray for Diagnostic Medical Imaging 

X-ray radiation is widely used today for diagnostic medical imaging, homeland security and industrial applications. Conventional x-ray source based on the original design of Roentgen and Coolidge is a single-pixel thermionic device with low spatial and temporal resolution and limited programmability, which hinders the performance of modern x-ray imaging systems. We have developed a new field emission x-ray technology based on the carbon nanotube field emitters. The new technology is capable of generating temporally and spatially modulated x-ray radiation that can be readily gated and synchronized with physiological signals. It has the potential to increase the resolution and scanning speed of today’s tomography scanners, and enable new imaging systems with new functionalities. Since the initial conception, the technology has moved from a simple laboratory curiosity to prototype production in commercial settings. 

In this talk we will introduce the nanotube x-ray technology. We will describe two imaging systems under development in our lab that utilize this unique x-ray technology. One is a dynamic micro-computed tomography (micro-CT) scanner for in-vivo imaging of small animal cancer models. The second is a stationary digital breast tomosynthesis system for in-vivo imaging of human breast cancer. Some other biomedical imaging and radiotherapy systems under development will be briefly described. 

June 17, 2008 Clark Auditorium

Kannan Krishnan, PhD
Campbell Chair Prof., Mat'l Sci & Eng
University of Washington

Biomedical Nanomagnetics: A Spin Through New Possibilities in Imaging, Diagnostics and Therapy 

Following a brief outlook on nanotechnology and an overview of our research, I will describe the ongoing development of nanomagnetic molecular probes (NMPs) with tailored properties, optimized for localized heating, MRI contrast enhancement and triggered drug release, and individually conjugated for specific functionality. Primary advantages of this class of NMPs are: a) the flexibility and precision with which the physical properties of the nanoparticle core -- size, size distribution, MRI relaxivity, magnetic relaxation dynamics and pH-sensitivity -- can be tailored and optimized. b) their functionality as ultrasmall and ultrasensitive MRI contrast agents with competitive performance suggesting lower dose and increased penetration. c) the optimized properties of these NMPs to generate heat locally and the therapeutic potential that this feature implies. d) their biocompatibility and very low cytotoxicity. e) their potential for translational application, primarily focused on detection and treatment of atherosclerosis and cancer. Finally, if time permits, preliminary results on the development of a magnetic particle imaging microscope -- an inexpensive, quantitative nanoimaging platform for meaningful dosimetry -- will also be presented.

June 19, 2008 Clark Auditorium

Bing Xu, PhD
Associate Professor, Dept. of Chemistry, Hong Kong Univ. of Sci. and Tech.

Design and Synthesis of Bionanomaterials for Applications from Outside to Inside of Cells 

This talk will focus on the development of two types of biofunctional nanostructures: (1) magnetic nanoparticles and (2) nanofibers formed by small therapeutic molecules. First, we will discuss the applications of magnetic nanoparticles for pathogen detections, protein separations, and intracellular manipulations. Compared to conventional used magnetic particles (with the sizes of 1-5 ?m) in biological separation or drug delivery, magnetic nanoparticles, combining with specific receptor-ligand interactions, confer high sensitivivity and selectivity for applications. Second, we will show the self-assembly of small molecules to form fibrillar nanostructures and result in hydrogels, which act as the scaffolds for potential biomedical applications such as wound healing, drug delivery, and inhibitor screening. Moreover, we will demonstrate the use of intracellular enzymatic reactions as a new way to triggers the self-assembly of hydrogelators and its potential applications for controlling the fate of cells.

July 15, 2008 Clark Auditorium

Kattesh Katti, MScEd, PhD, FRSC 
Professor of Radiology and Physics
University of Missouri

Green Nanotechnology In Medicine and Technology 

Nanoparticles are used in a myriad of applications from renewable energy, medical imaging, cancer therapy, in the design of smart materials, fast computers, heat transfer agents and as environmental restoration agents. As the nanotechnology revolution continues to unfold to unleash its power on our day to day lives, the environmental impacts of various nanotechnological production processes and finished products that are embedded with a wide spectrum of nanoparticles must be addressed right at the time of inception of this emerging technology. There is spawning fundamental and mission oriented research, in both academia and industry globally, toward applications of 100% \‘Green\’ nanotechnologies for the design and development of nanoparticles which in turn make their way into the design and development of smart electronic materials, life saving nanopharmaceuticals, environmental restoration technologies and in alternate green energy production devices. The sound economic models for hefty profits for the industrial corporations and their ability to perpetuate future Green nanotechnologies have created great niche for policy makers for future industrial and technological expansions. Green Nanotechnology is an interdisciplinary rapidly developing knowledge base at the interface of chemistry, physics, engineering and biological fields. Environmentally benign ‘Green’ nanotechnological processes are being developed to give the global corporate sectors the ability to design new products that are made from more eco - friendly materials including plants, crops, various phytochemicals and phytoconstructs, using processes that use less energy and generate less waste throughout the product lifecycle. This presentation will encompass description of latest discoveries from the speaker’s laboratories on the production of gold nanoparticles without the intervention of any ‘Man Made’ chemicals [1-4]. This lecture will encompass synthetic and biomedical aspects of gold nanoparticles produced via phytcohemicals, present in Soy and various plant origins. The applications of 100% ‘Green’ gold nanoparticles and green nanotechnologies in the design and development of new medical diagnostic/therapeutic agents, and biological sensors will be described.

August 19, 2008 Clark Auditorium

R. Bruce Weisman, PhD
Professor of Chemistry
Rice University

Near-infrared Fluorescence Imaging of Single-Walled Carbon Nanotubes in Biomedicine 

The unique physical and chemical properties of single-walled carbon nanotubes (SWCNTs) suggest promising applications in medical diagnosis, drug delivery, and thermal ablation therapy. Pristine SWCNTs are highly hydrophobic, but they can be stably suspended in aqueous media when noncovalently coated by artificial surfactants, DNA, RNA, or proteins. Because of their well defined π-electron states, most SWCNT structures emit intrinsic fluorescence at specific near-IR wavelengths between 900 and 1600 nm when excited by visible light. The minimal autofluorescence in this emission region allows SWCNTs in biological environments to be detected and imaged with very high sensitivity and selectivity. Moreover, SWCNTs are fluorophores offering unsurpassed photostability, large Stokes shifts, and an absence of blinking. Results will be described in which near-IR fluorescence methods have been used to monitor and track SWCNTs in cells, tissues, and organisms. In one project, macrophage cells were grown in the presence of SWCNTs. The resulting uptake of nanotubes was quantified by bulk fluorimetry and imaged by near-IR fluorescence microscopy. In an in vivo study, SWCNTs fed to Drosophila larvae were imaged in the living animals and in dissected tissues. In these tissue specimens it was possible to observe the location, orientation, and structural identities of individual nanotubes. A mammalian in vivo study explored the pharmacokinetics of SWCNTs after intravenous injection into rabbits, using near-IR fluorescence to selectively monitor nanotube concentrations. A circulation half-life of 1.0 hours was determined, and examination of tissue specimens taken 24 h after exposure revealed significant SWCNT concentrations only in the liver. Recent findings will also be presented on the properties of SWCNTs suspended in two new biocompatible noncovalent coatings: "PEG-eggs" (cross-linked amphiphile shells terminated with PEG molecules), and custom-synthesized multi-domain peptides. Prospects for future applications of SWCNT near-IR fluorescence in biomedicine will be discussed. 

August 28, 2008 Munzer Auditorium

Taeghwan Hyeon, PhD 
Director, National Creative Research Initiative Center for Oxide Nanocrystalline Materials
Professor, Chemistry and BioEngineering
Seoul National Univ

Large-scale Synthesis of Uniform-sized Nanoparticles and their Designed Assembly and Multifunctional Biomedical Applications 

We developed new generalized synthetic procedures to produce uniform-sized nanocrystals of many transition metals and their oxides without a size selection process (see review article: Angew. Chem. Int. Ed. 2007, 46, 4630). The synthesized nanocrystals include metals (Fe, Cr, Cu, Ni, and Pd), and metal oxides (γ-Fe2O3, Fe3O4, CoFe2O4, MnFe2O4, NiO, and MnO) and MnS). We report the ultra-large-scale (10s of grams) synthesis of monodisperse nanocrystals of magnetite and MnO from the thermolysis of metal-oleate complexes. We synthesized uniform-sized nanocrystals of various oxides of ZnO, TiO2, CeO2, Sm2O3 and FeOOH via non-hydrolytic sol-gel reactions. Clever combination of different nanoscale materials will lead to the development of multifunctional nano-biomedical platforms for simultaneous targeted delivery, fast diagnosis, and efficient therapy. In this presentation, I would like to present some of our group’s recent results on the designed fabrication of multifunctional nanostructured materials based on uniform-sized nanoparticles and their bio-medical applications. We developed a new T1 MRI contrast agent using biocompatible manganese oxide (MnO) nanoparticles, exhibiting detailed anatomic structures of mouse brain. We reported on the fabrication of monodisperse nanoparticles embedded in uniform pore-sized mesoporous silica spheres and PLGA polymers for simultaneous MRI, fluorescence imaging, and drug delivery. We fabricated magnetic gold nanoshells consisting of gold nanoshells (for NIR photothermal therapy) that are embedded with Fe3O4 nanoparticles (for MRI contrasting agent), and conjugated them with cancer targeting agent. We synthesized hollow magnetite nanocapsules and used them for both the MRI contrast agent and magnetic guided drug delivery vehicle. 

September 16, 2008 Clark Auditorium

Jonathan W. Simons, MD 
President and Chief Executive Officer
David H. Koch Chair
Prostate Cancer Foundation

Hypoxia Inducible Factor 1 in the Lethality of Prostate Cancer: A Nanotechnologies Applications Research Opportunity 

Lethal clones of prostate cancer express multiple genes involved in driving angiogenesis and genes critical to metastasis. Recently the signaling pathways, critical epigenetic factors, and genetic alterations involved in human prostate cancer angiogenesis have been elucidated. Hypoxia Inducible Factor 1 is a critical transcription factor associated with the clinical biology of the lethality of human prostate cancer and many other cancers. HIF-1 presents an ideal case study for nanotechnologies applications research. Furthermore, HIF-1 also appears to be involved in the overexpression of genes implicated in osseous metastasis. As the signaling pathways for HIF-1 have been identified, HIF-1 has become a new, compelling candidate therapeutic target in prostate cancer.

October 21, 2008 Clark Auditorium

Demir Akin, DVM, PhD 
Deputy Director
Stanford University

Prospects for Realization of Nanomedicine 

Dramatic changes occur in the material properties and unexpected behaviors emerge as the material dimensions approach nanometer size. Biological systems capitalize on these nanophenomena in the forms of naturally evolved life sustaining functions. Towards the realization of personalized medicine, nanotechnology promise amazing possibilities which can all be collectively named under Nanomedicine. In this talk, I will give some examples of these natural nanodevices and also some of our own man-made biomimetic micro to nanoscale nanomedical devices. As a highly cohesive, interdisciplinary group of researchers, we have been designing, fabricating and studying diagnostic and therapeutic applications of various BioMEMS and BioNEMS-based devices ranging from silicon-based nanocantilevers, nanopores to nanowires as biosensors, active biomimetic nanodevices that utilize phi29 DNA packaging machinery for novel biomolecule sensing, capture and sorting functions to novel multifunctional nanodevices utilizing microbal robotics (microbotics) for targeted delivery and controlled drug release. Systems level integration of a mixture of these modalities, as Lab-on-a Chip devices, will also be presented as well as some nanomaterials biocompatibility studies with ultra-nano- crystalline diamond (UNCD) as a novel material for biomedical devices. Brief but specific examples from each of these Nanomedicine domains will be given to convey our previous overall Nanobio activities in the hopes that this talk will lead us to explore future collaborative “nano-possibilities” under the umbrella of Stanford’s CCNE-TR

November 13, 2008 Clark Auditorium

Chad Mirkin, PhD 
Professor, Chemistry, Medicine,
Materials Science & Engineering
Director, International Institute for
Northwestern University

Nanostructures in Medicine 

We have recently reported new methods for the control of protein expression using oligonucleotide-functionalized gold nanoparticles. These “antisense particles”, as well as similarly functionalized siRNA particles, exhibit a range of unique properties that make them very well-suited for gene regulation. In particular, the particles are highly resistant to nucleases, exhibit high entry ability into multiple cell types as a result of their DNA shell, are generally non-toxic, and can be further modified with designer nucleic acids, siRNAs, and other chemical functionalities. These nanoparticle conjugates are capable of simultaneous cellular entry, semi-quantitative mRNA detection, and genetic control. The ability to control, characterize, and rationalize the properties of these materials is highlighted and represents exciting new opportunities in gene regulation and detection technologies. 

November 21, 2008 CISX Auditorium

Kang Choon Lee, PhD
Professor, Drug Targeting Laboratory
College of Pharmacy, SungKyunKwan University

Strategies of Peptide and Protein PEGylation and their Therapeutic Applications 

Recently, peptide and protein drugs have been attracted increasing promise in various therapeutic areas. However, their physicochemical and biological instabilities such as vulnerable enzymatic degradation, fast renal clearance, and generation of neutralizing antibodies remain as crucial obstacles for successful clinical applications, because these are directly related with short circulating half-life of peptide and protein drugs in the body. Similar to natural systems where the post-translational modifications (or conjugations such as acylation, methylation, and glycosylation) play important roles to create biologically or functionally new entity, numerous scientific efforts have been addressed to overcome the aforementioned problems associated with peptide and protein drugs. One of the most successful approaches is polyethylene glycol (PEG) conjugation, known as PEGylation.

PEGylation, first developed in the 1970s, is the pharmaceutical technology of covalent attachment of PEG to a drug, which improves the pharmacokinetic profile and leading to enhanced therapeutic effect. PEG is a water soluble, biocompatible, non-toxic polymeric material and PEGylation has been recognized for its important role in the effective application of medications, and it has been applied to proteins, peptides, oligonucleotides, antibody fragments, and small organic molecules, etc. In detail, the covalent attachment of PEG to peptide or protein drugs prolonged plasma half-life, reduce antigenicity and immunogenicity, increased physico-chemical stability, and prevented enzymatic degradation and/or inactivation. Still, numerous researches have been still striving to ensure product consistency of PEGylated drugs, including the efforts to improve PEGylated proteins and small molecules that have already reached in the market and PEGylation of novel medications, such as oligonucleotides and antibody fragments, for the intention to improve their bioavailability. Together with the research activities in the PEGylation filed, the continuous growth of the biopharmaceutical market implies that there is a bright future ahead for PEGylation technologies.

Recently, our researches have focus on the site-specific PEGylation of peptides or proteins for the improved therapeutic potentials in the area of osteoporosis, type 2 diabetes, cancers, rheumatoid arthritis, and growth malignancy. For those purpose, we tailored several serious of researches including selection of target peptide or proteins which are suitable for PEGylation with following improved therapeutic characteristics, optimization of PEGylation processes and positional isomer purifications and characterizations, and evaluations of pharmacokinetic and pharmacodynamic potentials.

In this presentation, I will briefly introduce the importance and potentials of PEGylation technology in the biopharmaceutical fields with my research experience in the peptide and protein PEGylation for the improved therapeutic potentials.

December 4, 2008 Alway Building, Room M106

Yoke Khin Yap, PhD 
Associate Professor, Physics
Michigan Technological University

Carbon, BN, ZnO, and Si Nanotubes: Growth, Properties, and Potential Applications 

Inorganic nanotubes represent a unique class of nanomaterials in which all atoms are located near the surface. Since electron flows on nanotubes are confined near the surface, nanotubes are especially attractive for electronics, chemical, and biological applications. In addition, their tubular structures enable nanofluidic and cellular drug delivery devices. In this colloquium, controlled growth of a series of inorganic nanotubes and the possible growth mechanisms will be discussed, in particular, vertically-aligned carbon nanotubes (CNTs), boron nitride nanotubes (BNNTs), ZnO nanotubes (ZnO NTs), and Si nanotubes (SiNTs). The roles of dissociative adsorption, tri-layer catalyst, reactive plasmas, nucleation controls, and growth vapor controls on the formation of these nanotubes will be emphasized. Structural, optical, and electronic properties of these nanotubes as well as their potential applications will be discussed.

December 16, 2008 Clark Auditorium

James Heath, PhD 
Elizabeth W. Gilloon Professor of Chemistry, CalTech
Professor, Molecular & Medical Pharmacology, UCLA
Director, NanoSystems Biology Cancer Center, CalTech

Technologies for Probing the Paradoxical Relationship of the Immune System and Cancer 

The human immune system has a complex relationship with cancer. On the one hand, it constitutes one of the most powerful weapons for battling the disease. On the other hand, many of the hallmarks of cancer are thought to arise out of processes in which the immune system actually reinforces the aberrant nature of cancer. A more general observation is that the presence of cancer is often accompanied by a broad inflammatory response that arises from the immune system/cancer interaction, and may be readily detected in the blood. In this talk, I will discuss work we are doing that is related to these various issues, and I will stress how a quantitative approach derived from fundamental physical sciences can provide a rapid pathway for connecting fundamental cancer biology to clinical applications. 

Sponsored by: Center for Cancer Nanotechnology Excellence Focused on Therapy Response (CCNE) Program - NIH/NCI U54 (MIPS)

Host: Director, Sanjiv Sam Gambhir, MD, PhD (sgambhir@stanford.edu)

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