Functionalized mesoporous silica via an aminosilane surfactant ion exchange reaction: controlled scaffold design and nitric oxide release
Nitric oxide-releasing mesoporous silica nanoparticles (MSNs) were prepared using an aminosilane-template surfactant ion exchange reaction. Initially, bare silica particles were synthesized under basic conditions in the presence of cetyltrimethylammonium bromide (CTAB). These particles were functionalized with nitric oxide (NO) donor precursors via the addition of aminosilane directly to the particle sol, and a commensurate ion exchange reaction between the cationic aminosilanes and CTAB. N-diazeniumdiolate NO donors were formed at the secondary amines to yield NO-releasing silica MSNs. Tuning of the ion exchange-based MSN modification approach allowed for the preparation of monodisperse particles ranging from 30 to 1100 nm. Regardless of size, the MSNs stored appreciable levels of NO (0.4-1.5 μmol/mg) with tunable NO-release durations (1-33 h) dependent on the aminosilane modification. The range of MSN sizes and NO release demonstrate the versatility of this strategy.
1. A method of producing nitric oxide (NO)-releasing mesoporous silica particles, wherein said method comprises:
reacting an alkoxysilane with an alkylammonium surfactant in the absence of added organoaminosilane to form a turbid mixture comprising mesoporous silica nanoparticles (MSN) in a colloidal sol;
adding an organoaminosilane to the MSN in the colloidal sol to modify the MSN via an ion exchange reaction of the organoaminosilane and an alkylammonium ion and form amino-functionalized MSN; and
reacting the amino-functionalized MSN with NO gas to produce NO-releasing MSN.
2. The method of claim 1 , wherein the alkoxysilane is one or more of tetraethylorthosilicate, methyltrimethoxysilane, ethyltrimethoxysilane, and isobutyltrimethoxysilane and the alkylammonium surfactant is a cetyltrimethylammonium halide.
3. The method of claim 2 , wherein the cetyltrimethylammonium halide is cetyltrimethylammonium bromide.
4. The method of claim 1 , wherein the ion exchange reaction is a cation exchange reaction.
5. The method of claim 1 , wherein the organoaminosilane is a compound of Formula I:
wherein z is 0, 1, or 2; and R 1 is
wherein R 2 and R 3 are each independently H, CH 3 , (CH 2 ) 2-5 NH 2 , or (CH 2 ) 2-5 NH(CH 2 ) 2-5 NH 2 .
6. The method of claim 1 , wherein the organoaminosilane is one or more of:
N-(2-aminoethyl)-3-aminopropyltrimethoxysilane,
N-(6-aminohexyl)aminopropyl trimethoxysilane,
(3-Aminopropyl)triethoxysilane,
N-methylaminopropyltrimethoxysilane,
and
(3-trimethoxysilyl-propyl)diethylenetriamine or combinations thereof.
7. The method of claim 1 , wherein the method produces the NO-releasing MSN via
a one-pot synthesis.
8. The method of claim 1 , wherein the NO-releasing MSN have a diameter-between about 30 nm and 1100 nm.
9. The method of claim 1 , wherein the NO-releasing MSN are substantially monodisperse in size.
10. The method of claim 1 , wherein the NO-releasing MSN have a diameter of about 30 nm, 150 nm, 350 nm and/or 1100 nm.
11. The method of claim 1 , wherein the alkylammonium surfactant is:
a. a linear alkylammonium salt having a structure of: [C n H 2n+1 (CH 3 ) 3 N] + Br − or [C n H 2n+1 (C 2 H 5 ) 3 N] + Br − where n=8, 10, 12, 14, 16, 18, 20, 22;
b. a geminal salt having a structure of: [C n H 2n+1 (CH 3 ) 2 N—(CH 2 ) 5 —N(CH 3 ) 2 —C m H m+1 ] + Br − where n=m=12, 14, 16, 18, 20, 22 and s=2-12; or
c. a divalent surfactant having a structure of: [C n H 2n+1 (CH 3 ) 2 N—C m H 2m+1 (CH 3 ) 3 N] 2+ where n+m=8, 10, 12, 14, 16, 18, 20, 22.
12. The method of claim 1 , wherein the NO-releasing MSN are insensitive to ambient humidity.
13. The method of claim 1 , wherein the amino-functionalized MSN have a polydispersity index (PDI) of less than 0.20.
14. A method of producing nitric oxide (NO)-releasing mesoporous silica particles, wherein said method comprises:
reacting an alkoxysilane with an alkylammonium surfactant to form mesoporous silica nanoparticles (MSN) in a colloidal sol;
adding an organoaminosilane to the MSN in the colloidal sol to exchange via an ion exchange reaction of the organoaminosilane and an alkylammonium ion to form amino-functionalized MSN; and
reacting the amino-functionalized MSN with NO gas to produce NO-releasing MSN,
wherein the amino-functionalized MSN have a polydispersity index (PDI) of less than 0.20.
15. A method of producing nitric oxide (NO)-releasing mesoporous silica particles, wherein said method comprises:
reacting an alkoxysilane with an alkylammonium surfactant to form mesoporous silica nanoparticles (MSN) in a colloidal sol;
adding an organoaminosilane to the MSN in the colloidal sol to exchange via an ion exchange reaction of the organoaminosilane and an alkylammonium ion to form amino-functionalized MSN; and
reacting the amino-functionalized MSN with NO gas to produce NO-releasing MSN;
wherein the alkoxysilane and the alkylammonium surfactant are reacted for at least 15 minutes before the addition of the organoaminosilane.