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Photodynamic Therapy for Neovasculature

12.09.2008

Are Two Photons Better than One? Non-linear Photoactivation for Micro-targeting of Cells and Vasculature

SPEAKER:
Brian Wilson, PhD:
Ontario Cancer Institute; University of Toronto

MODERATOR:
Irene Kochevar, PhD: MGH, HMS


  • Summary
  • Wikipedia
Are Two Photons Better than One?
Non-linear Photoactivation for Micro-targeting of Cells and Vasculature

Photodynamic therapy (PDT) refers to the treatment of disease with drugs activated by light.  The technique is currently used to treat diseases such as cancer and age-related macular degeneration (AMD).  Until recently PTD was only attempted using drugs activated by single photons, but researchers are currently investigating the possibility of performing PDT with drugs activated by two photons.  Researchers hope that two-photon PDT will someday allow doctors to treat diseases with greater accuracy and from a greater distance than is currently possible using single-photon PDT.

Many scientists believe that using two photons would be better than using only one because two-photon activation can be controlled more precisely than one-photon activation. Thus, using two photons instead of one would limit the amount of collateral damage caused by PDT.  Two-photon activation would also be preferable because it would depend on lower energy photons capable of penetrating deeper within tissue. 

A team of scientists led by Brian Wilson, PhD, has shown that near-infrared laser pulses on the femtosecond timescale can be used to activate currently available photosensitive drugs with two photons.  They also found that these drugs are capable of killing cells when activated by two photons under a confocal microscope.  Unfortunately, activating currently available drugs with two photons requires an impractical amount of light intensity.  High light intensity is required because the chance of two photons hitting the same molecule is very low unless there are a tremendous number of photons hitting the target.

In an attempt to make two-photon PTD clinically feasible, researchers are investigating new photosensitive drugs designed specifically to be activated by two photons.  One promising candidate is a porphyrin dimer.  Using two-photon activation, this molecule should theoretically be 500 times more effective than current drugs, but it has not yet been as effective as predicted because of problems related to its uptake and localization. 

In the future, researchers hope to optimize the effectiveness of two-photon PTD.  If advances are made, the technique could become an important therapy for diseases such as AMD, diabetic retinopathy, port-wine staining, and atherosclerosis.


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