Nitric oxide-releasing nanorods and their methods of use
View Patent ↗In one aspect, the subject matter disclosed herein is directed to NO-releasing functionalized nanorods having a desirable aspect ratio. The nanorods are also capable of releasing a desirable amount of NO (nitric oxide). In another aspect, the subject matter disclosed herein is directed to a composition comprising the NO-releasing nanorods. In another aspect, the subject matter disclosed herein is directed to methods of preparing NO-releasing nanorods having a specified aspect ratio. In another aspect, the subject matter disclosed herein is directed to a method of combating infection comprising administering to a subject a composition comprising NO-releasing nanorods, wherein the nanorods have a specified aspect ratio and NO-release profile.
1. A nitric oxide-releasing nanorod comprising,
i. a silane, and
ii. a functionalized mono, di or trialkoxysilane,
wherein said functionalized mono, di or trialkoxysilane comprises a NO-donor molecule;
wherein said nanorod has an aspect ratio of at least 1 and a [NO] max in a range of about 10 ppb/mg to about 16,000 ppb/mg.
2. The nanorod of claim 1 , wherein said nanorod is mesoporous.
3. The nanorod of claim 2 , wherein said mesoporous nanorod comprises pores having sizes from about 2 nm to about 50 nm in diameter.
4. The nanorod of claim 1 , wherein said silane has the formula Si(OR) 4 , wherein R is a C 1-5 alkyl.
5. The nanorod of claim 4 , wherein said silane is TEOS or TMOS.
6. The nanorod of claim 1 , wherein said silane is selected from the group consisting of methyltrimethoxysilane (MTMOS), ethyltrimethoxysilane (ETMOS), butyltrimethoxysilane (BTMOS), propyltrimethoxysilane (PTMOS), butyltriethoxysilane (BTEOS), and octadecyltrimethoxysilane (ODTMOS).
7. The nanorod of claim 4 , wherein said functionalized mono, di or trialkoxysilane is a nitric oxide functionalized N-(2-aminoethyl)-3-amino-isobutyl-dimethylmethoxysilane (AEAI); aminopropyldimethylethoxysilane (APDE); N-(6-aminohexyl)aminopropyltrimethoxysilane (AHAP3); N-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAP3); (3-trimethoxysilylpropyl)di-ethylenetriamine (DET3); (aminoethylaminomethyl)phenethyltrimethoxysilane (AEMP3); [3-(methylamino)propyl]trimethoxysilane (MAP3); N-butylamino-propyltrimethoxysilane(n-BAP3); t-butylamino-propyltrimethoxysilane(t-BAP3); N-ethylaminoisobutyltrimethoxysilane(EAiB3); N-phenylamino-propyltrimethoxysilane (PAP3); and N-cyclohexylaminopropyltrimethoxysilane (cHAP3).
8. The nanorod of claim 1 , wherein said aspect ratio is from about 4 to about 12.
9. The nanorod of claim 1 , wherein said aspect ratio is about 8.
10. The nanorod of claim 1 , wherein said nanorod has a [NO] max of from about 10 ppb/mg to about 14,000 ppb/mg.
11. The nanorod of claim 1 , wherein said nanorod has a [NO] max of from about 3,000 ppb/mg to about 7,000 ppb/mg.
12. The nanorod of claim 1 , wherein said nanorod has a length of less than about 1,700 nm.
13. The nanorod of claim 1 , wherein said nanorod has a length of from 100 nm to about 1,300 nm.
14. The nanorod of claim 1 , further comprising —(CH 2 CH 2 O) x — that is covalently bound to said functionalized mono, di, or trialkoxysilane, wherein x is an integer from one to 10,000.
15. The nanorod of claim 14 , wherein x is an integer from one to 50.
16. The nanorod of claim 1 , wherein said NO donor is selected from the group consisting of a diazeniumdiolate, nitrosothiol, a nitrosamine, a hydroxyl nitrosamine, a hydroxyl amine, a hydroxyurea, and combination thereof.
17. The nanorod of claim 16 , wherein said NO donor is selected from the group consisting of a diazeniumdiolate.
18. A method of preparing the nitric oxide-releasing nanorod of claim 1 , comprising:
a. contacting a silane with ammonia, sodium acetate, potassium acetate, sodium hydroxide or potassium hydroxide and mixtures thereof in the presence of a surfactant at a temperature T 1 ; to form a first composition;
b. allowing said first composition to age for a period of time, P, at a temperature T 2 to form a nanorod;
c. harvesting said nanorod;
d. contacting said harvested nanorod with a mono, di or trialkoxylsilane at a temperature, T 3 , to form an amine-functionalized nanorod;
e. harvesting said amine-functionalized nanorod;
f. contacting said harvested amine-functionalized nanorod with NO gas to form a nitric-oxide releasing nanorod; and
g. harvesting said nitric-oxide releasing nanorod.
19. A method of delivering nitric oxide to a subject, comprising:
administering an effective amount of said nitric oxide-releasing nanorod of claim 1 to said subject.
20. A method of treating a bacterial infection in a subject, comprising:
administering an effective amount of said nitric oxide-releasing nanorod of claim 1 to a subject in need thereof.