Compositions comprising a radiosensitizer and an anti-cancer agent and methods of uses thereof
A combination of an anti-cancer agent and a metal radiosensitizer potentiates the radiotherapy of cancer. Said anti-cancer agent is preferably cisplatin while the metal radiosensitizer is preferably gold nanoparticles. Both the anti-cancer agent and the metal radiosensitizer bind to DNA and potentiate the radiotherapy of cancer by synergistically increases the amount of double strand breaks induced by the radiation. The anti-cancer agent and the metal radiosensitizer may be encapsulated in liposomes.
1. A method of potentiating ionizing radiotherapy which produces low energy electrons comprising:
(a) administering to a subject in need thereof an effective amount of a composition comprising (i) an anti-cancer agent comprising platinum which binds to DNA and (ii) gold nanoparticles consisting of gold, and optionally, a stabilizer; and
(b) administering to the subject ionizing radiotherapy which produces low energy electrons,
wherein (a) occurs prior to (b); and
whereby (a) potentiates the ionizing radiotherapy of (b).
2. A method of enhancing ionizing radiosensitivity of a cell population to ionizing radiation which produces low energy electrons, comprising:
(a) exposing the cell population to an effective amount of a composition comprising (i) gold nanoparticles consisting of gold and optionally, a stabilizer and (ii) an anti-cancer agent comprising platinum and which binds to DNA; and
(b) exposing the cell population to the ionizing radiation which produces low energy electrons,
whereby (a) enhances the radiosensitivity of the cell population to the ionizing radiation of (b).
3. A method of increasing the amount of strand breaks in DNA in a cell exposed to ionizing radiotherapy which produces low energy electrons comprising:
(a) contacting the cell with an effective amount of (i) an anti-cancer agent comprising platinum which binds DNA and (ii) gold nanoparticles consisting of gold and optionally, a stabilizer; and
(b) submitting the cell to the ionizing radiotherapy which produces low energy electrons,
whereby the method results in increasing the amount of DNA strand breaks as compared to a method of applying the ionizing radiotherapy alone.
4. The method of claim 3 , wherein said anti-cancer agent comprising platinum is selected from the group consisting of cisplatin, carboplatin, oxaliplatin, and combinations thereof.
5. The method of claim 4 , wherein said anti-cancer agent comprising platinum is cisplatin.
6. The method of claim 3 , wherein said gold nanoparticles have an average diameter of between 1 and 60 nanometers.
7. The method of claim 3 , wherein said strand breaks are double strand breaks.
8. The method of claim 3 , wherein said anti-cancer agent and said gold nanoparticles are administered simultaneously.
9. The method of claim 3 , wherein said anti-cancer agent and said gold nanoparticles are administered separately.
10. The method of claim 8 , wherein said anti-cancer agent and said gold nanoparticles are encapsulated in liposomes.
11. The method of claim 10 , wherein a majority of said liposomes have a diameter of less than 400 nm.
12. The method of claim 10 , wherein a majority of said liposomes have a diameter between about 100 and about 150 nm.
13. The method of claim 12 , wherein said liposomes are coated with polyethylene glycol (PEG).
14. The method of claim 10 , wherein said liposomes preferentially target cancer cells.
15. The method of claim 14 , wherein said liposomes comprise dipalmitoyl phosphatidyl glycerol (DPPG), soy phosphatidyl choline, cholesterol and methoxy-polyethylene glycol-distearoyl phosphatidyl-ethanolamine (mPEG 2000 -DSPE).
16. The method of claim 14 , wherein said liposomes comprise dipalmitoylphosphatidylcholine (DPPC), 3β-[N—(N′,N′-dimethylaminoethane)-carbamoyl]-cholesterol (DC-Chol), Dioleoyl Phosphatidylethanolamine (DOPE) and polyethylene glycol (PEG).
17. The method of claim 15 , wherein said liposomes have a mean diameter of between about 70 nm to 152 nm.
18. The method of claim 10 , wherein the liposomes further comprise a stabilizer.
19. The method of claim 18 , wherein the stabilizer is polyacrylamide, dextrose, D-glucose or dithiolated diethylenetriaminepentaacetic acid (DTDTPA).
20. The method of claim 3 , wherein said gold nanoparticles have an average diameter of between 3 nanometers and 7 nanometers.