Method of controlled drug release from a liposome carrier
Disclosed are methods and compositions for the controlled release of a drug or agent from a liposome using light or radiation. Also disclosed are compositions comprising liposomes having a lipid layer, wherein the liposomes contain an agent, an enzyme capable of releasing the agent from the liposome, and an enzyme activator sequestered by a molecular cage. In another aspect, methods of delivering an agent to a target in a subject are disclosed.
1. A composition comprising a liposome having a lipid bi layer, the liposome containing
a) an agent;
b) phospholipase A2 or phospholipase C capable of releasing the agent from the liposome when in the presence of a calcium co-factor; and
c) a DM-Nitrophen sequestering the calcium co-factor capable of activating the phospholipase, wherein the calcium co-factor is required for activating the lipase.
2. The composition of claim 1 , wherein the molecular cage is photolabile.
3. The composition of claim 1 wherein the phospholipase A2 or phospholipase C is capable of hydrolyzing at least one lipid in the liposome.
4. The composition of claim 1 , wherein the agent comprises a chemotherapeutic agent, a polypeptide, a toxin, a radiotherapeutic agent, a radiosensitizing agent, an imaging agent or combinations thereof.
5. The composition of claim 1 , wherein the liposome further comprises a targeting molecule.
6. The composition of claim 1 , wherein the liposome further comprises at least one polypeptide capable of localizing to the lipid layer and a protease.
7. The composition of claim 1 , further comprising a nano-scintillator capable of emitting UV light upon excitation.
8. The composition of claim 7 , wherein the nano-scintillator is responsive to radiation.
9. The composition of claim 8 , wherein the nano-scintillator is responsive to X-radiation.
10. A method of delivering an agent to a target in a subject, the method comprising:
a) administering the liposome of claim 1 to the subject; and
b) exposing the target to light, whereby the light releases the calcium co-factor from DM-Nitrophen, the co-factor activates phospholipase A2 or phospholipase C and phospholipase A2 or phospholipase C releases the agent from the liposome.
11. A method of delivering an agent to a target in a subject, the method comprising:
a) administering the liposome of claim 7 to the subject; and
b) exposing the target to radiation, whereby the radiation activates the nano-scintillator to emit UV light which releases the calcium co-factor DM-Nitrophen, the calcium co-factor activates phospholipase A2 or phospholipase C and phospholipase A2 or phospholipase C releases the agent from the liposome.
12. The method of claim 10 , wherein the target comprises a tumor.
13. The method of claim 10 , wherein the liposome is administered to a patient before exposing the target to light.
14. The method of claim 11 , wherein the liposome is administered to a patient before exposing the target to radiation.
15. A method of controlled drug release, the method comprising the method of claim 10 , wherein the agent is released in a localized area.
16. A method of treating a condition responsive to the agent, the method comprising administering the liposome of claim 1 .
17. The method of claim 16 , wherein the condition is cancer.
18. The method of claim 11 , wherein the target comprises a tumor.
19. A method of controlled drug release, the method comprising the method of claim 11 , wherein the agent is released in a localized area.