Porphyrin Wires

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Porphyrin Wires as Pharmaceuticals
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porphyrins
Prof. Harry Anderson Oxford University
rotaxanes
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2nd EXCITED STATE
1st EXCITED STATE
Energy
400 nm
550 nm
GROUND STATE
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Benefits of two-photon absorption
absorption can be pin-pointedto very small
volumes
wavelength can be twicethat of one photon
excitation
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Visudyne (QLT Inc.) sales ca 200m in 2007
... but most chromophores have small two-photon
absorption cross-sections
www.goodhope.org.uk/eyedepartment
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The majority of photodynamic therapy drugs are
porphyrin-based ? typically harmless without
light ? catalytically produce toxic singlet
oxygen with light ? but limited selectivity for
diseased tissue
Two-photon absorption would benefit photodynamic
therapy ? exquisite control over treatment
volume ? improved treatment depths in tissue
? but the majority of PDT drugs are highly
inefficient at TPA
400 nm
Porphyrin dimers are efficient two-photon
absorbers ? can we make two-photon activated
drugs?
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Human ovarian epithelial adenocarcinoma cells
(SK-OV-3) red porphyrin dimer blue nucleus
(Hoechst 33258) green mitochondria (rhodamine
123)
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Phototoxicity to SK-OV-3 human ovarian cancer
cellsone-photon excitation at 657 nm, 10 µM
drug, 6 hr incubation
neither light nor drug wereindividually toxic at
these doses
Nature Photonics 2008, in press.
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Two-photon PDT efficacyas a function of laser
power, human ovarian cancer cells,
SK-OV-3 Tisapphire laser, 920 nm, 300 fs.
Photochem. Photobiol. 2007, 83, 1441.
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One-photon absorption 660 nm, 2.3 mW
Two-photon absorption 920 nm, 300 fs, 4.2 mW
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In vivo study window chamber model
Staton et al., Int. J. Exp. Path. 2004
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Staton et al., Int. J. Exp. Path. 2004
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in vivo
in DMF
In vivo fluorescence image
Nature Photonics 2008, in press.
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1.0 mm
Stereomicroscope imageTwo-photon irradiation?
920 nm,Ti-sapphire laser83 µm x 83 µm square,
40 µm deep
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200 µm
1.0 mm
Stereomicroscope imageTwo-photon irradiation?
920 nm,Ti-sapphire laser83 µm x 83 µm square,
40 µm deep
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Post-treatment
Pre-treatment
400 µm
400 µm
Nature Photonics 2008, in press.
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Before 0 min after 1 hr after
FITC 1.5 hr after Propidium iodide
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?
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Prof. Harry Anderson Oxford
Dr. Emma Dahlstedt Oxford
Karl Thorley Oxford
Dr. Grant Churchill Oxford
Dr. Milan Balaz Oxford
Prof. David Phillips Imperial College
Dr. Marina Kuimova Imperial College
Dr. Klaus Suhling Kings College, London
Dr. Aleksander Rebane Montana
Dr. Mikhail Drobizhev Montana
Prof. Brian Wilson Toronto
Dr. Aliaksandr Karotki Toronto
Adrian Mariampillai Toronto
Mamta Khurana Toronto
Dr. Eduardo Moriyama Toronto