Synergism of photodynamic and electropermeation effect on cell vitality as a novel cytotoxic agent
The present invention is based on the discovery that electroporation of a photosensitive agent in a cell and subsequent activation of the agent provides more effective killing of the electroporated cell than cells exposed to a photosensitive agent alone. The invention provides a method and apparatus for inhibiting cell growth or enhancing cell death. The method includes providing a photosensitive agent to a cell; applying an electric pulse to the cell of a sufficient strength and duration to electroporate the cell with the photosensitive agent; and applying light of an activatable wavelength to the cell thereby activating the agent and inhibiting cell growth or enhancing cell death.
1. A method for inhibiting cell growth or enhancing cell death comprising:
a) providing a photosensitive agent to a cell, wherein photosensitive agent is delivered as part of a pharmaceutically acceptable formulation that further comprises a pharmaceutically acceptable carrier and does not include liposomes;
b) applying an electric pulse to the cell of a sufficient strength and duration to electroporate the cell with the photosensitive agent; and
c) applying light of an activatable wavelength to the cell thereby activating the agent and inhibiting cell growth or enhancing cell death.
2. A method according to claim 1 , wherein multiple pulses are applied to the cell.
3. A method according to claim 1 , wherein the pulse amplitude is about 8410 kV/cm to about 6.0 kV/cm.
4. A method according to claim 1 , wherein the pulse width is about 0.1 milliseconds to about 10 milliseconds.
5. A method according to claim 1 , wherein the pulse is applied using at least two electrodes.
6. A method according to claim 5 , wherein at least one light conductor is combined with the electrode.
7. A method according to claim 6 , wherein the electrodes comprise at least two needle electrodes.
8. A method according to claim 7 , wherein the needle electrodes are heatable.
9. A method according to claim 1 , wherein the light is applied prior to, simultaneously with, or following the pulse.
10. A method according claim 1 , wherein the light is applied by a laser.
11. A method according to claim 1 , wherein the light is applied by a tungsten lamp.
12. The method at A method according to claim 1 , wherein the light is applied by a near ultraviolet lamp.
13. A method according to claim 1 , wherein the light has a wavelength of about 300 nm to about 950 nm.
14. A method according to claim 4 , wherein the amount of light applied is about 50 J/cm2 to about 1000 J/cm2.
15. A method according to claim 1 , wherein the light is applied extracorporeally.
16. A method according to claim 1 , wherein the photosensitive agent is a cytostatic agent.
17. A method according to claim 16 , wherein the cytostatic agent is selected from the group consisting of daunomycin, adriamycin and actinomycin.
18. A method according to claim 16 , wherein the photosensitive agent is 1 aevuline acid.
19. A method according to claim 18 , wherein the photosensitive agent is protoporphyrin IX.
20. A method according to claim 1 , wherein the method is performed in a subject.
21. A method according to claim 20 , wherein the subject is a human.
22. A method according to claim 1 , wherein the electrodes comprise meander electrodes.