Activated nitric oxide donors and methods of making and using thereof
Described herein are compositions useful in anticancer treatment. The compositions are composed of (a) an O 2 -aryl substituted diazeniumdiolate and (b) an amphiphile, wherein the amount of amphiphile is sufficient to produce a liposome or micelle. The compositions described herein provide numerous advantages such as increased solubility and stability of the O 2 -aryl substituted diazeniumdiolate in vivo. The compositions also do not induce hypotension. Methods for using the compositions in anticancer treatment are also described herein.
1. A method for treating cancer comprising administering to a subject a micelle composition comprising:
(a) O 2 -(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) or the pharmaceutically acceptable salt or ester thereof; and
(b) a poloxamer having the formula
HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H
wherein a is from 50 to 80 and b is from 10 to 25, and
wherein the cancer is leukemia.
2. The method of claim 1 , wherein a is from 50 to 70.
3. The method of claim 1 , wherein the amount of JS-K is less than 0.98% by weight of the micelle.
4. The method of claim 1 , wherein the amount of JS-K is less than 0.52% by weight of the micelle.
5. The method of claim 1 , wherein the composition does not induce hypotension.
6. The method of claim 1 , wherein the composition is administered parenterally, orally, subcutaneously, intralesionally, intraperitoneally, intraveneously, or intramuscularly.
7. A method for killing cancer cells comprising contacting the cancer cells with a micelle composition comprising:
(a) O 2 -(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) or the pharmaceutically acceptable salt or ester thereof; and
(b) a poloxamer having the formula
HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H
wherein a is from 50 to 80 and b is from 10 to 25, and
wherein the cancer cells are leukemia cells.
8. A method for reducing the growth of cancer cells comprising contacting the cancer cells with a micelle composition comprising:
(a) O 2 -(2,4-dinitrophenyl)1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate (JS-K) or the pharmaceutically acceptable salt or ester thereof; and
(b) a poloxamer having the formula
HO(C 2 H 4 O) b (C 3 H 6 O) a (C 2 H 4 O) b H
wherein a is from 50 to 80 and b is from 10 to 25, and
wherein the cancer cells are leukemia cells.