PURDUERESEARCH PARK

KPI: Kuiwon Choi (KIST)FPI: James F. Leary (Purdue Univ.)

Molecular Imaging and Nanomedicine for Theragnosis

using Nano-Biomaterials

Global Research Lab Program

PURDUERESEARCH PARK

Global Research Lab (GRL) The Global Research Laboratory (GRL) program was initiated by the Korea Foundation for International Cooperation of Science and Technology (KICOS) in 2006.

The GRL program has been designed to develop fundamental and original technologies through international collaborative research between Korean and foreign laboratories.

A proposal submitted for the GRL program should address a research topic which requires Korean and foreign research partners to engage in close collaboration for the attainment of significant scientific and technological goals.

PURDUERESEARCH PARK

Goals of GRL Program

GlobalResearch

Leader in KOREA

GlobalResearch

Lab. In KOREA

GlobalResearch Leader Networking

PURDUERESEARCH PARK

August, 20051st MOU between Biomedical Research Center (KIST) and Bindley Bioscience Center (Purdue)

September 7, 20061st Purdue-KIST collaborative symposium, entitled “Molecular Imaging and Nanomedicine”, was held at KIST.

March, 20072nd MOU between Life Science Division (KIST) and Bindley Biosciences Center (Purdue)

September, 20072nd Kist-Purdue collaborative symposium at Purdue Univ.

History of KIST-Purdue Univ. Collaboration

Dr. James F. Leary Dr. Kinam ParkDr. J. Paul Robinson Dr. Ji-Xin Cheng

PURDUERESEARCH PARK

Results of the Collaboration

Have been collaborating on joint researches for past 5 years

Successful scientist exchange: Seven young scientists from KIST joined Bindley Bioscience Center as post-doctoral fellows.

Some of them came back to Korea; Dr. J.H. Park (Kyung Hee Univ.) Dr. Y.W. Cho (Hanyang Univ.) Dr. K.M. Huh (Chungnam National Univ.) Dr. S.C. Lee (Korea Inst. of Ceramic Eng.&Tech.)

Recently, Dr. E.A. Kang (Purdue Univ.) from Purdue Univ. joined molecular imaging team in KIST as Post-Doc.

Publication activity between two labs: 10 papers, 7 book chapters

PURDUERESEARCH PARK

KPI: Kuiwon Choi (KIST)FPI: James F. Leary (Purdue Univ.)

Molecular Imaging and Nanomedicinefor Theragnosis using Nano-

Biomaterials

KIST-Purdue GRL Program

PURDUERESEARCH PARK

KIST-Purdue GRL Program

To develop original & fundamental technologies of “Theragnosis” throughKIST-Purdue complementary researchcollaborations.

To commercialize the technologiesthrough global network based on GRL.

To upgrade the KIST-Purdue GRL to the world class research center

PURDUERESEARCH PARK

Process and Result 7 GRLs were started in 2006.

5 GRLs were selected in 2007.

- Preliminary proposal was submitted in March.

- 4 proposals passed the 1st round of evaluation out of 20 proposals in BT area.

- 2nd round of evaluation (oral presentation for 1 hr.)was held in May.

Prof. Leary gave a great presentation despite ofhis severe backpain!

- The final 1 proposal was selected in May.

PURDUERESEARCH PARK

Future Medicine: TheragnosisTheragnosis : Therapy + DiagnosisNanomedicine and molecular imaging could be a strategic initiative to combine clinical and basic researches into a directed application toward theragnosis

Molecular ImagingMedical Information from imaging modality

Nanomedicine

Chemical drugDNA & ProteinImaging agents

PURDUERESEARCH PARK

Innovative Nano-Bio materials for Theragnosis

Biomarker for target cell

Cancer drugsEngineered genesTherapeutic proteins Photo sensitizer

Tracking optical probesPET or MR imaging probesSmart optical probes • Biological mechanism

• Live cell imaging• Live animal imaging• Drug delivery system• Engineered cell therapy• Early diagnostics• Drug screening in vivo• Targeted therapy

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Molecular Imaging

- Smart probes - Live cell imaging- Early diagnosis- High throughput drug screening - New imaging system

<2003, Technical Review, MIT>

cm mm μm nm

organ tissue cell DNA, protein

Molecular imaging is defined as the measurement and/or imaging of biological processes in living organism at the molecular and cellular level

PURDUERESEARCH PARK

- Nano-sized drug delivery- Molecular diagnosis- Nano biomaterials- Regenerative nanomedicine- Nano-scaled therapy

NanomedicineNanomedicine is the application of nanotechnology to the prevention and treatment of diseases in the human body

<2006, Technical Review, MIT>

PURDUERESEARCH PARK

Theragnosis in NTRM

Portfolio Analysis of Strategic Products and Functions Aiming at Bio-Healthtopia (NTRM, Vision II)

Eco

no

mic

Im

pact

Strategic Importance

very low low middle high very highvery low

low

middle

high

very high

Cell therapy

Prognostic systemvaccines

pulmonary

immune system

gene therapy

Cardivascular

diagnostics

anticancer drug

Rehabilitation system

medical imaging system

Nanomedicine

Molecular Imaging+

Theragnosis

PURDUERESEARCH PARK

Structure of GRL Program The collaboration between the KIST Biomedical Research Center and the Purdue Bindley Bioscience Center will be the most promising implement for theragnosis.

This research program will be the first program in the world which integrates molecular imaging and nanomedicine.

KIST Purdue Univ.Molecular Imaging

Nanomedicine

TheragnosisSmart imaging probe

Tumor targeting drug delivery

Fusion protein for cell imaging

Fluorescence optical imaging

Infrared imaging & therapy

Nano-factory for cell engineering

Drug delivery system for nanomedicine

Cytomics for nanomedicine

Nano-therapy and treatment

PURDUERESEARCH PARK

Status of Korean Research Lab

Principle Investigator Research Field

Original Technology Results

Dr. Kuiwon ChoiDr. Inchan Youn

New imaging modality

- Imaging software for imaging analysis- Infrared imaging modality- Microwave thermo-therapy

- paper; 76- patent; 15

Dr. Ick Chan KwonDr. Kwangmeyung Kim

Optical imaging

- Nano-sized drug delivery - Smart polymer-based probes

- paper; 110- patent; 45

Dr. Hyesung JeonDr. Hyungjun Ahn

Cellular imaging

- Reporter gene preparation - Live cell imaging with FRET technology - Electron Microscopy imaging

- paper; 30- patent; 5

Dr. Kuiwon Choi: The Korean Society of Biomechanics, Vice PresidentDr. Ick Chan Kwon: Korean Molecular Imaging Society, Vice President

Journal of controlled release (IF=3.696), Asian Editor

Structure and physiological function of the low density lipoprotein Receptor, Annual Review of Biochemistry (2005, IF=33.456)Polymeric Nanoparticles for Apoptosis Imaging, JACS (2006, IF=7.419)Polymeric nanoparticles for protein kinase activity, Chem Com (2007, IF = 4.426)Biopolymers for molecular imaging, Progress in Polymer Science (2007, IF=16.042)Protein phosphorylation-responsive polymeric nanoparticlesfor imaging protein kinase activities, Angewandte Chemie (2007, IF=9.956)

PURDUERESEARCH PARK

Status of Korean Research Lab

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Status of Korean Research Lab KIST Molecular Imaging Lab

KIST Regional Lab (Kyungbuk Medical School)

KIST Regional Lab (Asan Medical Center)

Principle Researcher: 2Senior Researcher: 4Post-Doc: 4Student: 9Researcher & Staff: 8

Near-infrared Microscopy

Fluorescent Microscopy

Imaging Box

Optical Tomography

ConfocalMicroscopy

Prof. Sangyun Kim, MDStaff: 5

Prof. In San Kim, MDStaff: 3

micro-PETAnimal room Clinical test Cyclotron for isotope labeling

PURDUERESEARCH PARK

Status of Foreign Research Lab

Principle Investigator

Research Field Original Technology Results

Dr. J. F. Leary - Nanomedicine- Regeneration nanomedicine- cancer treatment

- paper; 88- patent; 7

Dr. Kinam Park - Drug delivery system - Drug delivery system- Nanomedicine

- paper; 160- patent; 25

Dr. J. P. Robinson Dr. Ji-Xin Cheng

- Applied Cytomics- New imaging modality

- Cytomics- CARS imaging modality- Drug delivery system

- paper; 140- patent; 10

Dr. J. F. Leary: Purdue SVM Endowed Professor of NanomedicineFellow of the American Institute for Medical and Biological Engineering

Dr. Kinam Park: Showalter Distinguished Professor of Biomedical EngineeringJournal of controlled release, Editor-in-chief

Dr. J. P. Robinson: Current Protocols in Cytometry, Editor-in-chiefInternational Society for Analytical Cytology, President

Evaluation of disulfide reduction during receptor-medicated endocytosis by using FRET

imaging, Proceeding of the National Academy of Science (PNAS) (2006, IF=10.231)In situ sisualization of paclitaxel distribution and release by coherent anti-Stokes Ramanscattering microscopy, Anal Chem (2006, IF = 5.635)Mechanisms of controlled drug release from drug-eluting stents, Advanced Drug DeliveryRevies (2006, IF=7.189)In vitro and in vivo two-photon luminescence imaging of single gold nanorods, Proceeding ofthe National Academy of Science (PNAS) (2005, IF=10.231)

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Status of Foreign Research Lab Cover papers Books

World-wide software distributionMedia

PURDUERESEARCH PARK

Purdue BBC

Birck Nanotechnology CenterBiomedical Engineering

Professor: 4Post-Doc: 3Student: 6Researcher & Staff: 5

Bindley Bioscience Center (BBC)Bindley Bioscience Center (BBC)

Cytometry Instruments (Opto-injector, Cell sorter & Flow cytometry)

Confocal Microscope

Clean RoomMulti-photonConfocal Microscope

Coherent Anti-Stokes Raman Scattering Imaging BioMEMS

Status of Foreign Research Lab

PURDUERESEARCH PARK

1. Nano-Bio dot for microwave thermotherapy

Research Contents in KRL

Gold nanoparticles

normal SCC7tumor

Near IR Thermo MRI

Far IR thermo imaging

Diagnostic imaging

Microwave

Targeted MicrowaveThermotherapy

Thermomonitoring

MMP’s

• Near IR

• Thermo MRI

• Far IR thermo

PURDUERESEARCH PARK

100μm100μm

30 min30 min

Polymeric nanoparticle

Target molecule

Apoptosis & Protein Kinases Imaging Tumor Imaging OA & RA Imaging

2. Nano-polymeric particle smart probes for optical imaging

3. Nano-hybrid fusion protein for cellular imaging

Nuclear shuttling by fusion protein

Receptor-ligandinteraction imaging

Research Contents in KRL

PURDUERESEARCH PARK

1. Nano-factory for nanomedicine

Novel therapeutic gene regulation by genetic biosensor tethered to magnetic nanoparticles for the detection and treatment of retinopathy of prematurity

2. Nano-sized drug carriers for nanomedicine

Nano-sized drug carriers for tumor targeting

14day 15day 16day 17day9day 11day 12day 13day

0min 1day 2day 3day 4day 6day0min 1day 2day 3day 4day 6day 7day 8day

Tumor treatment with drug-loaded nanoparticles

Research Contents in FRL

PURDUERESEARCH PARK

3. Nano-hybrid materials for cytomics

4. Nano-bio probes for non-linear optical imaging

Multi-waved fluorescence materials for cell imaging and isolation

Development of Coherent Anti-Stokes Raman Scattering (CARS) microscopy

Probing the molecular composition of lipid membrane domains

Research Contents in FRL

PURDUERESEARCH PARK

KIST: Molecular Imaging

Purdue University: Nanomedicine

Nano-Polymeric Particle Smart Probes for Fluorescence Optical Imaging Project Leaders: Dr. I.C. Kwon and Dr. K. Kim

Nano-Hybrid Fusion Proteins for Cellular ImagingProject Leaders: Dr. H. Jeonand Dr. H.J. Ahn

Nano-Bio Dot for Microwave ThermotherapyProject Leaders: Dr. K. Choiand Dr. I.C. Youn

Nano-Factory for Cell Engineering Project Leaders: Prof. James F. Leary

Nano-Sized Drug Carriers for NanomedicineProject Leaders: Prof. K. Park

Nano-Hybrid Materials for CytomicsProject Leaders: Prof. J. Paul Robinson

Nano-Bio Probes for Non-linear Optical ImagingProject Leaders: Prof. Ji-XinCheng

Nano-Bio materials for Theragnosis

- Nano-Bio probes for molecular imaging & drug delivery system

- Nano-Bio hybrid fusion proteinfor cytomics & medical imaging

- Nano-Bio dot for cancer imaging & treatments

- Nano-Bio factory for molecular imaging and cell engineering

Global Research Lab

Research Networking

PURDUERESEARCH PARK

Research Schedule for 1st and 2nd Year No. Stage I: Synthesis Nano-Bio materials for Molecular Imaging and

Nanomedicine (1st year)Month

0 6 12 18 24

Review of patents and papers in 19901Output: Reports for theragnosis

-------- -

Synthesis of nanoparticle optical probe for molecular imaging 2Output: optical probes for cancer diseases (2ea)

---------- ------------ ---------

Synthesis of nanoparticle optical probe for molecular imaging 3Output: fusion protein probes for apoptosis & protein kinases (2ea)

------------ ----------- ----------- ---------

Preparation of Nano-Bio dots for cancer imaging and therapy 4Output: gold particle-based probes (2ea)

----------- ----------- ----------

Synthesis of Nano-sized drug carriers & Nano-factor for Nanomedicine5Output: nano-sized drug carriers (2ea), Nano-factor (1ea)

------- ----------- ---------

Preparation of Nano-sized probes for cytomics & Non-linear opticalimaging

6Output: nano imaging probes for cytomics & non-linear optical imaging(3ea)

------------- ------------- ----------

No. Stage II: Evaluation of Nano-Bio materials in cell-based screening system as new imaging probe & (2nd year)

Month 0 6 12 18 24

Cell-based screening of molecular imaging probes1Output: molecule imaging probes for cellular imaging (5ea)

------------ ---------

Therapeutic efficacy measurements of nano-sized drug carriers, nanofactory, gold particles in cellular based screening

2

Output: Data sheet for therapeutic efficacy in cellular based screening

----------- ------------- ---------

Cytotoxicity of nano-bio materials for molecular imaging probes and 3Output: Data sheet for cytotoxicity of new materials

------------- ----------

PURDUERESEARCH PARK

Technical Roadmap

Smart Imaging Nano-Probes

Fusion Gene/Protein forImaging/Medicine

Multi-Func.Drug Carriers

High-Throughput Drug Screening

New Imaging System for Early Diagnosis Molecular-Based Nano-Therapy Nano-factory for

Nanomedicine

2007 2008 2009 2010 2011 2012 2013 2014 2015

Platform Tech. for Theragnosis

Innovative Fusion Tech. for Theragnosis

Applied Tech. for Theragnosis

Nano-Bio Hybrid Probes for Molecular Iamaging

Fusion Gene/Protein Synthesis

Nano-sized Drug Carriers

Nano-Factory for Nanomedicine

Nano-Dot for Nano-Therapy

New Imaging System for Theragnosis

industry

PURDUERESEARCH PARK

Strategy for GRL Program

- Set up GRL in KIST & Purdue Univ.- Nano-Bio Materials Bank- Young Scientist Exchange Program- International Symposium - Internet Meeting - Global Networking

GRL in Purdue Univ.

GRL in KIST Internet meeting

PURDUERESEARCH PARK

Current Participant Researchers

Participant researchersKIST27

2 principal scientists, 4 senior scientists, 4 postdoctoral fellows, 9 graduate students, 8 technicians

Purdue Univ.

18

4 professors, 3 postoctoral fellows, 6 graduate studuents, 5 technicians

PURDUERESEARCH PARK

Research Budget

Direct Budget (US$)

GRL Program 550,000 $/ year3 yrs + 3 yrs + 3yrs (3 stages)

KISTIntramural Fund

Funds to Purdue Univ. for GRL Research

PURDUERESEARCH PARK

Global Research Leader in

Theragnosis

GRLGlobal Research Laboratory

Innovative Nano-Bio materials

Molecular Imaging Labin KIST

Nanomedicine LabIn Purdue Univeristy

Thank You for Your Attention