Synergism of photodynamic and electropermeation effects on cell vitality as a novel cytotoxic agent
First Claim
1. A method for inhibiting cell growth or enhancing cell death, comprising:
- (a) providing to a cell a pharmaceutically acceptable formulation that comprises a photosensitive agent and a pharmaceutically acceptable carrier, provided that the photosensitive agent is not encapsulated in liposomes;
(b) applying an electric pulse of a sufficient strength and duration to electroporate the cell to facilitate entry of the photosensitive agent into the cell; and
(c) applying light of a photoactivating wavelength to the cell, thereby activating the photosensitive agent and inhibiting cell growth or enhancing cell death.
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Abstract
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.
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Citations
20 Claims
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1. A method for inhibiting cell growth or enhancing cell death, comprising:
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(a) providing to a cell a pharmaceutically acceptable formulation that comprises a photosensitive agent and a pharmaceutically acceptable carrier, provided that the photosensitive agent is not encapsulated in liposomes;
(b) applying an electric pulse of a sufficient strength and duration to electroporate the cell to facilitate entry of the photosensitive agent into the cell; and
(c) applying light of a photoactivating wavelength to the cell, thereby activating the photosensitive agent and inhibiting cell growth or enhancing cell death. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 15)
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11. A method for treating a cell proliferative disorder in a subject comprising:
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(a) administering to a subject, optionally a human, having or suspected of having a proliferative disorder a pharmaceutically acceptable formulation comprising a pharmaceutically acceptable carrier and (i) a photosensitive agent, provided that the photosensitive agent is not encapsulated in liposomes, or (ii) a plurality of different photosensitive agent species, wherein at least one of the photosensitive agent species is a photooxidizing agent;
(b) applying an electric pulse of a sufficient strength and duration to electroporate cells of the subject to facilitate entry of the agent(s) into said cells, wherein the electric pulse is applied using at least two electrodes, optionally at least two meander electrodes;
(c) prior to, simultaneously with, or following the electric pulse, applying light of a photoactivating wavelength to said cells to activate the agent(s) to effect treatment of the cell proliferative disorder; and
, optionally, at least one of (i) a sensitizing agent, optionally aevuline acid, and (ii) a visualizing agent. - View Dependent Claims (12, 13, 14, 16, 20)
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17. A method, comprising:
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(a) providing to a cell a photooxidizing agent and at least one of a sensitizing agent and a visualizing agent;
(b) prior to, simultaneously with, or following provision of the agents to the cell, applying an electric pulse to the cell of a sufficient strength and duration to electroporate the cell with the agents; and
(c) applying light of a photoactivating wavelength to the cell, thereby activating the photooxidizing agent to inhibit cell growth or enhance cell death, wherein the method is used for (i) inhibiting cell growth or enhancing cell death or (ii) treating a cell proliferative disorder. - View Dependent Claims (18, 19)
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Specification