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Upconversion Nanoparticles For Photodynamic Therapy

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by

Amira T-Apollon

on 4 September 2014

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Transcript of Upconversion Nanoparticles For Photodynamic Therapy

Cancer
Photodynamic Therapy (PDT)
Design Verification
Upconversion Nanoparticles For Photodynamic Therapy
Advisors:
Dr. Gang Han
Dr. Marsha Rolle

Design Objectives
Design Verification
Presenter:
Amira Tokatli-Apollon

Uniform cubic core/shell structures
Average diameters ~ 26 (± 1.7) nm
5-Aminolevulinic Acid (ALA)-UCNP Conjugation
ALA Conjugation Confirmation (FTIR)
N-H Bending
NH3 Stretching vibration
-N=C- Hydrazide bond (ALA-UCNP)
Full acid-sensitive covalent linkage
Carboxyl group
Surgery
Radiotherapy
Chemotherapy
Current Treatments
Limitation
Complications
Causes local damage
Causes systemic toxicity
1,660,290 Expected new cases
585,720 Expected death/ year
Minimal invasiveness
Specific targeting
Low cost
Few side effects
Advantage
Acknowledgments
Conclusion
Scale Bar = 100nm
70% Decrease in cell viability over 10 minutes of NIR Laser (1 W/cm2) exposure
PDT Poor Deep Tissue Penetration
Upconversion Nanoparticles (UCNPs)
Fluorescence Intensity of DCFDA
(Measures The Production of Singlet Oxygen)
University of Massachusetts Medical School
Biochemistry and Molecular Pharmacology Department
Dr. Gang Han
Amol Punjabi
Xiang Wu
Yuanwei Zhang
Worcester Polytechnic Institute
Dr. Marsha Rolle
Biomedical Engineering Department
26nm
Worcester Polytechnic Institute
Amira Tokatli-Apollon
Biomedical Engineering Department
Any Questions?
Red wavelength
980nm
Prodrug 5-Aminolevulinic Acid (ALA)
650nm
Red 650nm
NIR 980nm
Upconvert NIR light into
strong red visible light
Deliver ALA to
Cancer Cells
Stable ALA conjugation to
activate photosensitizer
Size and Uniformity
CaF2 shell particle
Diameter 20~40nm.
Need
Need
Emission Spectra Under 980nm 1w/cm2 Excitation
Step #2
Synthesizing the Ln-based upconverting nanoparticle core
Need
Increase the red-emission for more efficient photodynamic therapy
Strategy
Increase the Yb ratio
Step #3
Conjugating ALA to the UCNPs
Need
Covalent bond to avoid pre-leaking of ALA
Strategy
Use a hydrazone linkage which breaks in the cell
Transmission Electron Microscopy (TEM)
25nm
26nm
26nm
28nm
Cell Proliferation Assay with 980 nm wavelength NIR Laser (MTT)
Fluorescence Intensity of DCFDA
(Measures The Production of Singlet Oxygen)
Tissue
Maximum red emission
UCNP size and uniformity

ALA with 980nm NIR light
Kills the cancer cells
1.2 cm penetration depth
MTT Assay With Various Tissue Thickness
Thank You
Future Works
Test the effectiveness of longer NIR laser exposure

Use actual skin tissue for penetration experiment

Maximize tissue thickness for penetration experiment

Utilize In-vivo testing with animal model
Step #1
ALA
UCNP
Capable of Upconverting
NIR to Red Visible Light
Project Goal
Extend the application of PDT to deepest cancer cells by using alternative NIR light to trigger singlet oxygen generation.
Need
Red-emission enhancement
Flurometric comparison
Size distribution of hydrophilic upconverting
Tissue
American Cancer Society, "Cancer Facts & Figures 2013." 4 Sept. 2012a. Web. 26 Sept. 2013. <http://www.cancer.org/research/cancerfactsfigures/cancerfactsfigures/cancer-facts-figures-201>
o Castano, A. P., Mroz, P., & Hamblin, M. R. (2006). Photodynamic therapy and anti-tumour immunity. Nature Reviews Cancer, 6(7), 535-545.
Haase, M., & Schäfer, H. (2011). Upconverting nanoparticles. Angewandte Chemie International Edition, 50(26), 5808-5829.
Idris, N. M., Gnanasammandhan, M. K., Zhang, J., Ho, P. C., Mahendran, R., & Zhang, Y. (2012). In vivo photodynamic therapy using upconversion nanoparticles as remote-controlled nanotransducers. Nature Medicine.
Dougherty, T. J., Gomer, C. J., Henderson, B. W., Jori, G., Kessel, D., Korbelik, M., ... & Peng, Q. (1998). Photodynamic therapy. Journal of the National Cancer Institute, 90(12), 889-905.
Ytterbium Oxide; MSDS No. 96772 [Online]; Acros Organics N.V.: Fair Lawn, NJ, July 20, 2009, http://www.jtbaker.com/msds/englishhtml/d7120.htm
Cost Breakdown Chart
30% Decrease in cell viability over 20 minutes of NIR Laser (1 W/cm2) exposure with 12 mm tissue thickness
ALA converts to the photosensitizer PpIX in the cell which can then be activated for cancer therapy. In normal cells, PpIX is immediately degraded by the enzyme ferrochelatase, so it cannot be activated for therapy, but in cancer cells, ferrochelatase is underexpressed. Therefore, the PpIX stays in the tumors longer and can be activated for therapy.
http://www.intmedpress.com/serveImage.cfm?sUID=3e4c3ded-e20c-4d78-be99-a90b9c282720
Because it has been shown in studies that the tissue vasculature of tumors makes it more possible for particles in the nano size range to enter tumors by something called the enhanced permeation and retention effect (EPR). This is where the whole hype of nanoparticles in cancer came from.
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