Activatable Molecular Probes for Optical Imaging Ick Chan Kwon, - - PowerPoint PPT Presentation

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Activatable Molecular Probes for Optical Imaging Ick Chan Kwon, - - PowerPoint PPT Presentation

Jul 27, 2023 159 likes •513 views

Activatable Molecular Probes for Optical Imaging Ick Chan Kwon, Ph.D. KIST-DFCI On-Site-Lab Dept. Cancer Biology, Dana Farber Cancer Institute Biomedical Research Institute Korea Institute of Science & Technology 22 Sep, 2019 The 16th

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Ick Chan Kwon, Ph.D.

KIST-DFCI On-Site-Lab

  • Dept. Cancer Biology, Dana Farber Cancer Institute

Biomedical Research Institute Korea Institute of Science & Technology

OA Normal

+ Probe

  • Inhibitor

OA Normal

+ Probe + Probe + Probe

OA Normal

+ Probe

  • Inhibitor

OA Normal

+ Probe + Probe + Probe

Activatable Molecular Probes for Optical Imaging

22 Sep, 2019 The 16th U.S.-Korea Forum on Nanotechnology Qualcomm Institute, University of California, San Diego, CA, USA

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Therapeutic Effect

Aspirin

COX (cyclooxgenase) inhibitor

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Therapeutic Effect

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Evaluation of Therapeutic Efficacy

JNCI 2014

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The left image shows MRI scans of a patient harboring 2 brain metastases

  • f a lung carcinoma. Both tumors

were treated in a 1 hour treatment session using Cyberknife radiosurgery. The right image shows the first MRI control 4 weeks after treatment. Both tumors are completely eliminated. The left image shows a tumor of the lung before Cyberknife

  • treatment. A small (5 mm) fiducial

was implanted for real time breath triggered robotic treatment. The right image shows the result 2 weeks after the single session Cyberknife procedure. The tumor is already reduced in size and shows a central necosis. Photos from website of cyber-knife.net

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Molecular Medicine Molecular Therapy

Photos from : Lore Leighton, Laboratory of John Kuriyan Photos from MIT open course 5.36 Biochemistry Laboratory

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Bioconjugate Chemistry, 22 (2011) 125

Visualize Apoptosis

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Molecular Imaging

Visualization of biological process Molecular events at molecular and cellular level In living systems Using remote imaging detectors “The characterization and measurement of biological processes in living animals, model systems, and humans at the cellular and molecular level by using remote imaging detectors”

Lucker GD and Piwnica-Worms D Acad. Radiol. 2001;8;4

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Strongly quenched state Signals Amplified State Protease

Nanoparticles for Activatable Probe

Polymeric Nanoparticles NIR Dye Quencher Substrate

  • MMP

+ MMP

Probe concentrations

Quenching properties MMPs specificity in vitro

0.55 1.1 2.2 5.5 11 MMP-2 Conc. mmol/L

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No treat MMP-2 Probe + inhibitor MMP-2 Probe

1 h 2 h 1 h 2 h

In vivo image (eXplore Optix)

1: Tumor: SCC7 2: MMP-2 probe: 5 mg/kg 3: MMP-2 inh.: 100 µg/kg

HT1080 LLC B16F10 SCC7

MMP-9 MMP-2

Nanoparticles for Activatable Probe

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Cathepsin B-specific nanoprobe (CB-NP) for cancer

Abs

400 500 600 700 800 0.0 0.5 1.0 1.5 CB-NP 0.8µM CB-peptide probe 20µM CB-peptide probe 10µM CB-peptide probe 5µM CB-peptide probe 2.5µM

Abs Wavelength (nm)

UV absorbance

Ryu et al. Journal of Materials Chemisry 2011;21;17631

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Real-time imaging of autophage in living cells

Design of activatable probe Specificity test against Atg4 protease Cellular uptake of FITC-labeled probe Fluorescence microscopy under autophagy condition induced with rapamycin or starvation

Ahn HJ et al, Autophage 2011

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Albumin-conjugated MMP nanoprobe for cancer

GGKGRVGLPG

Albumin

GPLGVRGKGG

Human Serum Albumin(HSA)

  • conjugated Probe

10 20 30 40 50 60 500 1000 1500 2000 2500

MMP2 MMP3 MMP7 MMP9 MMP13 inhibitor

Fluoresence intensity (a.u.) Time (min)

500 600 700 800 0.0 0.5 1.0 1.5

HSA-MMP probe 1.8µM MMP probe 20µM MMP probe 10µM MMP probe 5µM MMP probe 2.5µM

Abs Wavelength (nm) HSA-MMP

  • Inhibitor

MMP-2 Fluorescence (Cy5.5) +Inhibitor

1h 3h 9h 24h

HSA-MMP MMP-peptide probe HSA-MMP + inhibitor

MMP-peptide probe HSA-MMP +inhibitor

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Biomimetic Cage protein for Apoptosis Imaging

Design of Cy5.5-HspDEVD-BHQ3 Apoptosis imaging using cage probe In vivo biodistribution of cage probe Caspase specificity test

Therapeutic evaluation of anticancer drug using cage nanoprobe Ahn HJ et al, Biomacromolecules 2011

TEM analysis

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Target Protein for Apoptosis

Membrane Cytoplasm Caspase-3

Caspase-12 Caspase-6 Caspase-7 Caspase-9 Cyto-c

Smac/ Diablo XIAP Survivin

Capase-8/10

P

Lamin A α-Fodrin PARP

ER Stress Ca++ FADD Death Stimuli

DFF

FasL, TNF-α Caspase-3

Caspase-3 is a member of the interleukin-1beta converting enzyme (ICE) family of cysteine proteases

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Visualize Apoptosis

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  • Cellular uptake

10 20 50 µg/mL Probe Concentration (µg/ml)

  • Cellular viability

Visualize Apoptosis

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Visualize Apoptosis

Bioconjugate Chemistry, 22 (2011) 125

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SLIDE 20

Bioconjugate Chemistry, 22 (2011) 125

Visualize Apoptosis

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Stem Cell Labeling and Tracking

  • S. Lee et al. / Biomaterials 139 (2017) 12-29
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  • S. Lee et al. / Biomaterials 139 (2017) 12-29

Stem Cell Labeling and Tracking

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SLIDE 23
  • S. Lee et al. / Biomaterials 139 (2017) 12-29

Stem Cell Labeling and Tracking

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  • S. Lee et al. / Biomaterials 139 (2017) 12-29

Stem Cell Labeling and Tracking

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  • S. Lee et al. / Biomaterials 139 (2017) 12-29

Stem Cell Labeling and Tracking

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  • S. Lee et al. / Biomaterials 139 (2017) 12-29

Stem Cell Labeling and Tracking

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In vivo T-cell distribution (without Tumor) Ex vivo T-cell distribution

Biodistribution of Cy5.5 labeled splenocytes in vivo

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Cell Labeling and Tracking

  • SW. Kang et al. / Theranostics, 14 (2014) 420-431
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Cell Labeling and Tracking

  • SW. Kang et al. / Theranostics, 14 (2014) 420-431
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Cell Labeling and Tracking

  • SW. Kang et al. / Theranostics, 14 (2014) 420-431
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Cell Labeling and Tracking

  • SW. Kang et al. / Theranostics, 14 (2014) 420-431
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Enzyme Specific Cell Labeling

  • MK. Shim et al. / Angew Chem Int Ed, 55 (2016) 14698-14703
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Enzyme Specific Cell Labeling

  • MK. Shim et al. / Angew Chem Int Ed, 55 (2016) 14698-14703
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Enzyme Specific Cell Labeling

  • MK. Shim et al. / Angew Chem Int Ed, 55 (2016) 14698-14703
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Thank You !

Financial Support from KIST “Intramural Research Program” MOST “Real Time Molecular Imaging”