Nov 2007 Volume 1, Issue 4 Programs of Excellence in ...Bao), we have used Tat peptide-conjugated...

1Volume 1, Issue 4Nov 2007

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Programs of Excellence in Nanotechnology

Topic focus: Second Annual Inter-PEN Meeting

IN THIS ISSUE

5 Meet our PEN 6 Spotlight 9 Upcoming

Events 12 2nd Annual Inter-PEN

Meeting in Santa Barbara14 Reflections

PEN members in attendance at the 2nd Annual Inter-PEN Conference, on the campus of University of California Santa Barbara, October 19-21, 2007.

Second

Annual

Inter-PEN

Meeting

N a t i o n a l H e a r t , L u n g & B l o o d I n s t i t u t e

The recent 2nd Annual Inter-PEN meeting, hosted by The Burnham Institute/UCSB PEN at the

beautiful UCSB campus, represents an important milestone, roughly the mid-point of the fi ve year funding period for the PEN program. Having reviewed each of the PENs earlier in the year, I was impressed by the increasing rate of progress, and the rapid strides that have taken place in that short time. Each of the PENs is making unique contributions to the nanomedicine fi eld. For example, the systematic approach to nanoparticle toxicity from the MGH/Harvard PEN represents the fi rst attempt that I am aware of to develop rapid screens and use hierarchical clustering to glean information on what determines the toxicity of nanoparticles. The Washington University group is making important strides in understanding the relationship between nanoparticle structure and the kinetics and route of plasma clearance. At the Burnham, the studies on platelet-mimicking nanoparticles and their adherence to substrate in fl ow chambers will lead to better understanding and design of adherent circulating particles. At Georgia Tech/Emory, the combination of nanotechnology and bioengineering

is giving insight into the relationship between shear stress and atherosclerotic plaque development, an area of critical interest for NHLBI and the cardiovascular fi eld. There was also increasing evidence of interactions between the PENs, taking advantage of the strengths of each of the groups, again a welcome development.

The second morning of the meeting featured a fascinating workshop on nanofabrication and nanoassembly, with several of the UCSB faculty giving up their Sunday mornings to talk about their work. This gave an interesting insight into what’s going on in other areas of nanotechnology. Finally I’d like to thank James Lee and Jeff Smith from The Burnham Institute and Eileen Cler from Washington University for their contributions to organizing this highly enjoyable and p r o d u c t i v e meeting.

Attendees

posters

2 Volume 1, Issue 4 Nov 2007

EMORY UNIVERSITY, GEORGIA TECHN a n o t e c h n o l o g y : D e t e c t i o n & A n a l y s i s o f P l a q u e F o r m a t i o n

Imaging and Tracking of Bioconjugated Quantum Dots

in Living Cells

By Gang Ruan, Amit Agrawal and Shuming Nie

Department of Biomedical Engineering([email protected])

Bioconjugated semiconductor quantum dots (QDs) are a new class of fl uorescent probes under intense research and

development for broad applications in molecular, cellular, and in vivo imaging. The basic rationale is that these nanometer-sized particles have unique functional and structural properties, such as size and composition tunable fl uorescence emission, large absorption cross sections, and exceptional brightness and photostability compared with organic dyes and fl uorescent proteins. Recent research has achieved considerable success in using QDs for labeling fi xed cells, tissue specimens, and for imaging cell membrane proteins. However, only limited progress has been made in developing QD probes for molecular imaging inside living cells. A major problem is the lack of effi cient methods for delivering monodispersed (that is, single) QDs into the cytoplasm of living cells. A common observation is that QDs tend to aggregate inside living cells, and are often trapped in organelles such as vesicles, endosomes, and lysosomes. As a result, little is known about the interactions of QDs with intracellular proteins and their transport behavior inside living cells, limiting the use of nanoparticle probes in cardiovascular biology and medicine.

At the Georgia Tech and Emory PEN (PI: Gang Bao), we have used Tat peptide-conjugated QDs (Tat-QDs) as a model system to examine the cellular uptake and intracellular transport of

nanoparticles in live cells [1]. Derived from the HIV-1 Tat protein, the Tat peptide has emerged as a novel cellular delivery vector for a wide range of cargos, due to its excellent delivery effi ciency and minimal cytotoxicity. Considerable effort has been devoted to understanding the delivery mechanism of this cationic carrier. The delivery process was initially thought to be independent of endocytosis because of its apparent independence on temperature. However, later research showed that the earlier work failed to exclude the Tat peptide conjugated cargos bound to plasma membranes, and was largely an artifact caused by cell fi xation. More recent studies based on improved experimental methods indicate that Tat peptide mediated delivery occurs via macropinocytosis, a fl uid-phase endocytosis process that is initiated by Tat-QD binding to the cell surface. These new results, however, did not shed any light on the downstream events or the intracellular behaviors of the internalized cargos. This kind of detailed and mechanistic investigations would be possible with QDs, which are suffi ciently bright and photostable for extended imaging and tracking of intracellular events. In addition, most previous studies on Tat peptide mediated delivery are based on the use of small dye molecules and proteins as cargos, so it is not clear whether larger nanoparticles would undergo the same processes of cellular uptake and transport. This understanding is needed for the design and development of imaging and therapeutic nanoparticles, which is a major goal of the NHLBI nanotechnology program.

We have used a spinning-disk confocal microscope for dynamic fl uorescence imaging and tracking of quantum dots in living cells at 10 frames per second. The results indicate that the peptide-conjugated QDs are internalized by macropinocytosis, in agreement with the recent work of Dowdy and coworkers. It is interesting however that the internalized


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Tat-QDs are tethered to the inner surface of vesicles, and are trapped in intracellular organelles. An important fi nding is that the QD loaded vesicles are actively transported by molecular machines (such as dyneins) along microtubule tracks to an asymmetric perinuclear region called the microtubule

organizing center (MTOC). Furthermore, we fi nd that Tat-QDs strongly bind to cellular membrane structures such as fi lopodia, and that large QD-containing vesicles are able to pinch off from the tips of fi lopodia. These results not only provide new insights into the mechanisms of Tat peptide mediated delivery, but also are important to the development of nanoparticle probes for intracellular targeting and imaging.

Figure 1 shows time-dependent fl uorescence

images of cultured HeLa cells when incubated with Tat-QD nanoparticles for a 24-hour period. Within 5 minutes of Tat-QD addition, the cell outer surfaces (including fi lopodia and plasma membranes) were visibly stained. At 30 min, Tat-QDs started to appear inside the cells, but remained close to the cell peripheries. At one

hour of incubation, the fi lopodial bridges (membrane channels between adjacent cells) were also labeled (highlighted by a box), and a small number of Tat-QDs were accumulated at a unique intracellular region (highlighted by a circle). Although they are not a focus in this study, fi lopodial bridges are involved in retrovirus travel from infected cells to healthy ones. For the internalized QDs, a striking feature was a gap region between the cell peripheries and their accumulation site where there were no or few Tat-QDs detected. This indicates

that the intracellular transport of Tat-QDs is mediated by an active process because passive diffusion would lead to a random distribution of Tat-QDs in the cytoplasm. From 1 hr to 24 hrs, more and more Tat-QDs were transported and accumulated at this intracellular region, with fewer and fewer Tat-QDs on the cell surface. By 24 hrs, essentially all the Tat-QDs had accumulated at the intracellular region. There were minimal adverse effects on cell

Figure 1. Time-dependent imaging of Tat-QD uptake and intracellular transport in cultured HeLa cells over a 24-hour period. New cell culture plates were used for each time point, and multiple views were randomly acquired by using a spinning-disk confocal microscope at a rate of 10 frames per second. These changes were found to minimize the effects of lamp and laser illumination on cultured cells. In the image taken at 1 hour, QD-stained fi lopodial bridges are highlighted with a rectangular box, and the microtubule organizing center (MTOC) is indicated with a circle.

functions, which remained normal for at least 3 days. This intracellular region corresponds to the microtubule organizing center (MTOC), a distinct region that is responsible for attaching and organizing the microtubules in living cells.

To confi rm that the MTOC is indeed the site for QD accumulation, we have used GFP-encoded MCF-7 cells (stably expressing GFP-tubulin) and have found that QDs and tubulins are spatially colocalized in a perinuclear region (just outside the cell nucleus).

Dynamic fl uorescence imaging further reveals that most of the endocytosed Tat-QDs are actively transported to an intracellular region just outside the nucleus, while directed motion also occurs along cell peripheral tracks (Figure 2). The motion of Tat-QDs from the cell periphery toward the perinuclear region is most likely caused by microtubule-dependent transport, an active process that is mediated by molecular motors such as dyneins. The destination of this transport is the microtubule organization center (MTOC). In addition to inward motion, we also observed directed motion from the perinuclear region to the cell periphery, a process that is probably mediated by different molecular motors such as kinesins.

The fact that eventually Tat-QDs were all accumulated at the perinuclear region suggests that the inward motion is dominant. The average speed of the trajectories shown in Figure 2a was determined to be 1.0 μm/s, similar to the

value reported for dynein motors under in vitro conditions. The second class of directed motion (that is, along cell peripheries) probably arises from microtubules that lie along the cell peripheries, but it is also possible that myosin motors carry Tat-QDs along actin fi laments.

References1. Gang Ruan, Amit Agrawal, Adam I. Marcus and Shuming Nie. “Imaging and tracking Tat peptide-conjugated quantum dots in live cells: New insights into nanoparticle uptake, intracellular transport, and vesicle shedding”, in press, J. Am. Chem. Soc. (2007).

Figure 2. Direct observation of active transport of endocytosed Tat-QDs inside living cells. (a, b): Directed motion from the cell periphery to an intracellular region adjacent to the cell nucleus. The red box area of image (a) is magnifi ed in image (b). The white line is the trajectory of one Tat-QDs vesicle pointed by the red arrow (Supplementary Video 1, frame 21 to 29, frame rate 249 ms/frame). The green line shows the plasma membrane boundary of the cell. (c, d): Directed motion along cell peripheral tracks. The red box area of image (c) is magnifi ed in image (d). The white line is the trajectory of one Tat-QD vesicle pointed by the red arrow (Supplementary Video 2, frame 5 to 13, frame rate 249 ms/frame). The green line shows the plasma membrane boundary of the cell.



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Save the DateSave the Date

Our Pro j ec t Manager s

Emory University

Our Co - Inve s t i ga tor s

Program Official Denis BuxtonPrincipal Investigator

Gang Bao

Charles Searles

Xiaoping HuMark Goodman

Dongmei (May) Wang

Georgia Tech

W. Robert Taylor

Hanjoong Jo

Shuming Nie

Niren Murthy

Don Giddens

Wayne Alexander Kathy Griendling

David Harrison

Emory University and The Georgia Institute of Tech-nology will host the 3rd Annual Inter-PEN Meet-ing in Atlanta, Georgia on October 10-11, 2008.

* All images were provided courtesy of Emory University and The Georgia Institute of Technol-ogy


P E N S P O T L I G H T O N :W U S T L S e n i o r I n v e s t i g a t o r , D a n i e l P . S c h u s t e r , M . D .

Daniel P. Schuster, Professor of medicine and radiology at Washington University School of Medicine, died,

Sept. 11, 2007 while playing racquetball. He was 57. Dan was a major force in the PEN project at Washington University. Dan was a leader at Washington University as a physician-scientist, educator, clinical, basic researcher, and administrator. He was a highly innovative and creative in his thinking and research. Upon his arrival at Barnes-Jewish hospital in 1981, he formalized the practice of critical care medicine and was the fi rst recipient of the Virginia E. & Sam J.

Golman Chair in Critical Care Medicine. He quickly took advantage of the expertise at Washington University to develop a research program in lung imaging during injury and disease and has been a leader in that fi eld, adapting PET imaging for the lung, and in the past decade, developing molecular imaging methods. Dr. Schuster served as Associate Dean in Clinical Studies and was Associate Dean for Clinical Research since 1999. He served the University in many capacities, on countless committees. He also was the author over 160 scholarly articles, book chapters, and editor of a book, “Translational and Experimental Clinical Research.” Dan attended the University of Michigan (BS, 1972) and Yale University (MD, 1976). He trained in internal medicine at Parkland Memorial Hospital in Dallas, Texas Southwestern University, and was a fellow in the Critical Care Medicine. Dan was married to Debra Klein Schuster, a lawyer specializing in elder care, and had two children, Evan 15, and Jamie, 17. A memorial in his honor was held at Washington University, on Monday October 22, 4:00 PM at the Eric P. Newman Auditorium on the Medical Center Campus.

In Memory of Dan Schuster

The PEN Team Members under Dan Schuster were Steve Brody, Matt Bernstein and Chris Sher-man, all of WUSTL. Dan also collaborated with John Taylor, Raffaella Rossin, Michael J. Welch, Ke Zhang and Karen L. Wooley of WUSTL, as well as Adah Almutairi, Jessica Cohen and Jean Fréchet of UCB.


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P E N S P O T L I G H T O N :M G H / H a r v a r d S e n i o r I n v e s t i g a t o r , M a t t h i a s N a h r e n d o r f , M . D .

Matthias Nahrendorf, M.D., joined the Center for Molecular Imaging Research at the Massachusetts General Hospital in 2004

and is a staff member and Instructor in Radiology at the Harvard Medical School. He graduated from medical school at Heidelberg University and London University, and completed his residency and Internal Medicine Fellowship at Wuerzburg University Hospital. As part of a pioneering team directed by Axel Haase, he worked on the development and application of MRI based imaging tools for rat and mouse cardiovascular phenotyping.

Since joining CMIR, his main focus has been the molecular imaging of atherosclerosis and infarct healing. Together with his colleagues, he has discovered the importance of the transglutaminase Factor XIII in the suffi cient healing of myocardial infarcts, and in the prevention of heart failure. In a dynamic and highly interdisciplinary team lead by Ralph Weissleder, Dr. Nahrendorf has worked on the noninvasive detection of atherosclerotic lesions, using optical, magnetic resonance and nuclear imaging approaches. “Our aim is to detect an infl amed, so called vulnerable plaque before it ruptures and clogs the artery, in order to stop the number one killer in the western world, myocardial infarction and stroke.” Towards this goal, he has used targeted probes that report on key players in the infl ammatory cascade known to be crucially involved in plaque development, and multimodal imaging strategies.

For more information about Matthias Nahrendorf’s research, visit the CMIR web site at http://cmir.mgh.harvard.edu/faculty/Matthias_Nahrendorf.html.

Matthias Nah-rendorf and Jean Fréchet, a Senior Investigator from the University of California Berke-ley, at the Inter-PEN Meeting in Santa Barbara, California, Octo-ber 19-21, 2007.

Fluorescence Tomography and Magnetic Resonance Imaging of

Myocardial Macrophage Infi ltration in

Infarcted Myocardium In Vivo1

By Jason McCarthy, Ralph Weissleder

([email protected])

Until recently, fl uorescence imaging of the heart has been limited to invasive in vivo applications, such as intravi-

tal fl uorescence microscopy, or ex vivo appli-cations. The ability to perform multispectral detection of fl uorescent probes non-invasively within the heart will allow for the simultane-ous imaging of several biological processes with high throughput. To this end, Drs. Sosnovik and Nah-rendorf at the Center for Mo-lecular Imaging Research have utilized fl uorescence molecular tomography (FMT) to localize macrophage infi ltration within a mouse model of myocardial infarction. In this study, the authors utilized the avidity of macrophages towards fl uores-cently labeled, dextran-coated iron oxide nanoparticles (CLIO-Cy5.5) to localize macrophage infi ltration in infarcts by both MRI and FMT imaging mo-dalities. Myocardial infarction was induced by complete coronary ligation of the left coronary artery, while in the sham surgery (control), the artery was exposed without ligation. Two days after infarction, the mice were injected intrave-nously with CLIO-Cy5.5 and imaged. MRI of the infarcted mice demonstrated left ventricular

dilation with thinning of the ventricular walls. Consistent with contrast agent uptake, negative contrast effects could be visualized in the myo-cardium. As compared to the control mice, the contrast to noise ratio was 5-fold higher in the infarcted mice. Accumulation of CLIO-Cy5.5 was also observed by FMT (fi gure 1). While both groups of mice demonstrated fl uorescence emission related to hepatic uptake of the agent, the infarcted mice demonstrated marked in-creases in fl uorescence from the heart (0.57±0.1 versus 0.28±0.04). These fi ndings were further correlated with ex vivo fl uorescence refl ectance imaging (mean fl uorescence intensity of infarct-ed mice = 125.0±30.6 ; of control = 45.2±6.5). Histology of the infarcted hearts revealed in-fl ammatory cell infi ltrate (Mac-3) within the wound, which co-localized with areas of fl uo-rescence intensity from the nanoagent, a fi nd-ing that is consistent with the known uptake of

CLIO. This study has demonstrated that FMT can indeed be utilized to image fl uorescently-labeled probe uptake within the heart, and that the uptake of a multimodal nanoparticle can be imaged by both MR and fl uorescence imaging modalities. The imaging of myocardial mac-rophage infi ltration in vivo has the potential


M G H , H A R VA R D , M I T , B W HT r a n s l a t i o n a l P r o g r a m o f E x c e l l e n c e i n N a n o t e c h n o l o g y

to be of signifi cant value in both research and clinical settings and may play an important role in the study of postinfarction healing as well as other conditions such as myocarditis, heart failure, and transplant rejection.1

ReferencesSosnovik, D. E.; Nahrendorf, M.; Deliolanis, N.; Novikov, M.; Aikawa, E.; Josephson, L.; Rosenzweig, A.; Weissleder, R.; Ntziachris-tos, V. “Fluorescence tomography and mag-

netic resonance imaging of myocardial mac-rophage infi ltration in infarcted myocardium in vivo.”, Circulation 2007, 115(11), 1384-1391.


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The Four PENs and

their Principal Investigators

Nanotechnology: Detection & Analysis of Plaque

FormationEmory University

Georgia Institute of Technology

P.I. - Gang Bao, Ph.D. Director , Emory-GT, Program of Excellence in

Nanotechnology

CoE Distinguished Professor

The Wallace H. Coulter Department of

Biomedical Engineering

Georgia Institute of Technology

Emory University

Nanotherapy for Vulnerable PlaqueThe Burnham Institute

University of California Santa Barbara

The Scripps Institute

P.I. - Jeff rey W. Smith, Ph.D.

Professor

Director, Center on Proteolytic Pathways

Director, Program of Excellence in

Nanotechnology

Burnham Institute for Medical Research

Translational Program of Excellence in

NanotechnologyHarvard University

Massachusetts General Hospital

Massachusetts Institute of Technology

Brigham and Women’s Hospital

P.I. - Ralph Weissleder, M.D., Ph.D. Director, Center for Molecular Imaging Research

Professor of Radiology, Harvard Medical School

Massachusetts General Hospital

Integrated Nanosystems for Diagnosis and TherapyWashington University in Saint Louis

University of California Santa Barbara

University of California Berkeley

P.I. - Karen L. Wooley, Ph.D.

James S. McDonnell Distinguished University

Professor in Arts & Sciences

Professor, School of Arts & Sciences,

Department of Chemistry

Professor, School of Medicine,

Department of Radiology

Faculty member in the

Center for Materials Innovation

Third Annual Inter-PEN Meeting

October 10-11, 2008

Hosted by Gang BaoEmory University

Georgia Institute of TechnologyAtlanta, Georgia

Executive Committee Meetings

2007 - December 7

2008 - March 7 June 13 September 5 December 5

UPCOMING EVENTS

for2007 - 2008

Authors(Left) Jason McCarthy(Right) Ralph WeisslederMassachusetts General HospitalHarvard University


U C S B , U C B a n d W U S T LI n t e g r a t e d N a n o s y s t e m s f o r D i a g n o s i s a n d T h e r a p y

In vivo evaluation of novel PEGylated Nanoparticles

for Imaging and Drug Delivery

By Eric D. Pressly, Raffaella Rossin, Aviv Hagooly, Ken-ichi Fukukawa,

Benjamin W. Messmore, Karen L. Wooley, Michael J. Welch*, and Craig J. Hawker*

([email protected], [email protected])

A fundamental limiting factor in the use of nanomaterials for diagnosis and treatment of disease in vivo is

the premature removal of nanomaterials by the reticuloendothelial system (RES), mainly in the liver and spleen. However, coating a nanoparticle with poly(ethylene glycol) (PEG) has been shown to reduce the uptake by the RES and increase their circulation time in blood.1 In an Intra-PEN collaboration between the Hawker and Welch groups in the WU-UCSB-UCB PEN, novel polymer nanoparticles displaying a PEG corona were developed and tested in vivo for their pharmacokinetic properties

using radiopharmaceutical techniques.Amphiphilic comb copolymers were developed with a hydrophobic poly(methyl methacrylate) (PMMA) backbone, functionalized with a derivatized form of DOTA (1,4,7,10–te t raazocyclododecane-N,N’ ,N”,N’’’ -tetraacetic acid) and PEG branches. These polymers were shown to form multi-molecular micellar aggregates in water as shown schematically in Scheme 1.2 The sizes of the PEG branches were 1.1 kDa, 2 kDa, and 5 kDa, with the different PEG lengths resulting in variations of the hydrodynamic diameters of the nanostructures, from 10 to 20 nm, as confi rmed by dynamic light scattering and cryo-transmission electron microscopy.2 Incorporation of the positron emitting radionuclide, 64Cu, into the DOTA ligands in these nanostructures allowed for tracking of their in vivo behavior by small animal PET and biodistribution techniques. Through these studies, a direct correlation between PEG length and the blood circulation time was found. Increased PEG chain sizes in the nanoparticles from 1.1 kDa to 2 kDa and 5 kDa resulted in longer blood retention times

and lower liver uptake values.2 Small animal PET/CT co-registered images (Figure 1) of these radiolabeled nanostructures at 1, 4, and 24 h p.i. clearly show this trend as the intensity of the heart increases and the liver decreases

Scheme 1: Structural representation of comb copolymers and their multi-molecular nano-particle structure in water.

“However, coating a nanoparticle with poly(ethylene glycol) (PEG) has been shown to reduce the uptake by the RES and increase their circulation time in blood.1”


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with PEG length at all time points. These results have been used to develop structure/biodistribution relationships among nanomaterials in this NHLBI-PEN (HL080729).

References1. (a) Owens III, D. E.; Peppas, N. A., “Opsonization, Biodistribution, and Pharmacokinetics of Polymeric Nanoparticles,” International Journal of Pharmocology 2006, 307, 93-102. (b) Lee, C. C.; MacKay, J. A.; Fréchet, J. M. J.; Szoka, F. C.,“Designing Dendrimers for Biological Applications,” Nature Biotechnology 2005, 23, 1517-1526.2. Pressly, E. D.; Rossin, R.; Hagooly, A.; Fukukawa, K.-I.; Messmore, B. W.; Welch, M. J.; Wooley, K. L.; Lamm, M. S.; Hule, R. A.; Pochan, D. J.; Hawker, C. J. “Structural Effects on the Biodistribution and Positron Emission Tomography (PET) Imaging of Well-Defi ned 64Cu-Labeled Nanoparticles Comprised of Amphiphilic Block Graft Copolymers.” Biomacromolecules 2007, 8, 3126-3134.

Figure 1: Co-registered small animal PET/CT coronal slices of Balb/C mice injected with 64Cu -labeled comb copolymer nanostructures at 1, 4, and 24 hpost injection (adapted and re-printed from Biomacromolecules 2007, 8, 3126-3134. Copyright 2007 American Chemical Society).

Authors

Eric PresslyUC-Santa Barbara

Aviv HagoolyWashington University

Raff aella RossinWashington University

Karen L. WooleyWashington University

Michael J. WelchWashington University

Craig J. HawkerUC-Santa Barbara

Benjamin W. MessmoreUC-Santa Barbara

Ken-ichi FukukawaUC-Santa Barbara


Second Annual Inter-PEN Meeting

(Below) Emory University’s Bob Taylor with Postdoc, Natalia Landazuri and Ph.D. Candidate, Nick Willett.

(Right) The BurnhamInstitute’s Hui Xie,

David Valenta, Sheryl Harvey and

Kunal Gujraty.

(Right) Stanley Shaw

of Harvard and MIT.

University of California Santa BarbaraOctober 19-21, 2007

(Above) Ph.D. Candidates, Randy Ankeny of Hanjoong Jo’s group and Jamie Mells of Bob Taylor’s group, both from Emory/Georgia Tech.


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(Above) Alisar Zahr and Jean-Luc Fraikin of UCSB take a break between lectures to look at the posters presented by the other PENs.

(Left) WUSTL PEN members Monica Shokeen, Raffaella Rossin, Aviv Ha-gooly, and Caro-lyn Anderson and Georgia Tech PEN member Charles Glaus (second from the right) discuss their collaboration on nanoparticles for dual MRI/PET imag-ing of express-ing lesions.

(Right) WUSTL Ph.D. candidate, Yali Li explains to UCSB postdoc Ryosuke Sakai, the emerging new chemistry for controlled drug delivery, including pH-responsive and thermo-responsive SCKs and HBFP-baesd nanoparticles for 19F MRI.

Poster Session

(Right) UCSB Ph.D. candidates Poorn-ima Kolhar and Nishit Dosni re-view the research presented during the poster session.

Congratulations: (Left to Right) Charlie Glaus (Georgia Tech), Monica Shokeen (WUSTL), Adah Almutairi (UCB), Donwon Lee and Kousik Kundu (Georgia Tech) were recognized for their posters and their out-standing contributions to their PENs.

(Above) Craig Hawker of UCSB offers the selection of prizes to Postdoc, Adah Almutairi, of UCB, and to Kousik Kundu (Right) of Georgia Tech.

After a full day of lec-tures, dinner was served in the courtyard outside of the Engineering Sci-ences Building. During the Poster Session, PIs from the four PENs nomi-nated Ph.D. candidates and Postdocs for receiv-ing a small award.

αvβ3


NHLBI Inter-PEN QuarterlyNHLBI Inter-PEN Quarterlywww.nhlbi-pen.net

Program Official

Denis Buxton

National Heart, Lung, and Blood Instituteemail: [email protected]://www.nhlbi.nih.gov

Principal Investigators

Gang Bao

Emory UniversityGeorgia Institute of TechnologyEmail: [email protected]://pen.bme.gatech.edu/

Jeffrey W. Smith

The Burnham InstituteThe Scripps Research InstituteUniversity of California, Santa BarbaraEmail: [email protected]://www.pennvp.org

Ralph Weissleder

Harvard UniversityMassachusetts General HospitalMassachusetts Institute of TechnologyBrigham and Women’s HospitalEmail: [email protected]://cmir.mgh.harvard.edu/nano/nano-tpen.

php?menuID_=223

Karen L.. Wooley

Washington University in Saint LouisEmail: [email protected]

Production Designer, Editor, Photographer

Eileen A. Cler

Web Designer and DeveloperProgram Coordinator for NHLBI-PEN GrantWashington University in Saint LouisEmail: [email protected]

from the Inter-PEN Meeting in Santa Barbara:

2ND ANNUAL INTER-PEN MEETINGS a n t a B a r b a r a , C a l i f o r n i a O c t o b e r 1 9 - 2 1 , 2 0 0 7

"It was obvious from the presentations, post-ers and discussions that each PEN has made significant advances over the past year, toward the development of their individual nanoscale materials and approaches to probe and treat pulmonary and cardiovascular diseases. Moreover, the skills development activities that have been accomplished and collaborative interactions that are emerging add fur-ther to the broader impacts of these unique programs." - Karen L. Wooley

“The research from each PEN is moving at a fast pace and has clear translational poten-tial. Given the exciting data presented, it should not be unexpected to see a number of projects proceed to the clinic within the next few years.” - Ralph Weissleder

“The science contributed by each of the PENs has the ability to act as a catalyst for our own research, opening up possibilities that, up until now, may not have been obvious.” - Jason McCarthy

Slides from the Second Annual Inter-PEN Meeting at the University of California in Santa Barbara are available on the Inter-PEN website under “Slides” at

www.nhlbi-pen.net.

If you would like a copy of the group photo from the Sec-ond Annual Inter-PEN Meeting, please send an email to Eileen A. Cler at “[email protected]”. You will recieve both a high and a low resolu-tion JPG fi le.

R E F L E C T I O N S

(Right) The Inter-PEN Meeting in Santa Barbara was organized by James Lee (and Principal Investigator, Jeffrey W. Smith) of The Burnham Institute and also facilitated by Eileen A. Cler of Washington University in Saint Louis.

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