Functionalized Mesoporous Silica via an Aminosilane Surfactant Ion Exchange Reaction: Controlled Scaffold Design and Nitric Oxide Release

Abstract

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.

What is claimed is: 
     
         1 . NO-releasing mesoporous silica particles, wherein the NO-releasing mesoporous silica particles are charged with NO at a concentration of at least about 0.4 μmol/mg and release NO with a half-life for release of the NO that is no less than about 2 minutes. 
     
     
         2 . The NO-releasing mesoporous silica particles of  claim 1 , wherein the mesoporous silica particles are substantially monodisperse in size. 
     
     
         3 . The NO-releasing mesoporous silica particles of  claim 1 , wherein the mesoporous silica particles have a diameter in a range of about 30 nm to about 1100 nm. 
     
     
         4 . The NO-releasing mesoporous silica particles of  claim 1 , wherein the NO-releasing mesoporous silica particles are made by a process that comprises generating a mesoporous silica particle by reacting tetraethylorthosilicate with a cetyltrimethylammonium halide to generate a cetyltrimethylammonium ion; and exchanging via an ion exchange reaction the cetyltrimethylammonium ion for an organosilane molecule. 
     
     
         5 . The NO-releasing mesoporous silica particles of  claim 4 , wherein the organosilane 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 NO-releasing mesoporous silica particles of  claim 5 , wherein the organosilane is one or more of:
 aminosilane 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 NO-releasing mesoporous silica particles of  claim 1 , wherein the NO-releasing mesoporous silica particles have a half-life for release of the NO that is no less than about 25 minutes. 
     
     
         8 . The NO-releasing mesoporous silica particles of  claim 1 , wherein the NO-releasing mesoporous silica particles have a polydispersity index (PDI) of less than 0.20. 
     
     
         9 . NO-releasing mesoporous silica particles having a polydispersity index (PDI) of less than 0.20. 
     
     
         10 . The NO-releasing mesoporous silica particles of  claim 9 , wherein the NO-releasing mesoporous silica particles comprise a diazeniumdiolate-functional group. 
     
     
         11 . The NO-releasing mesoporous silica particles of  claim 9 , wherein the NO-releasing mesoporous silica particles have a diameter in a range of about 30 nm to about 1100 nm. 
     
     
         12 . The NO-releasing mesoporous silica particles of  claim 11 , wherein the NO-releasing mesoporous silica particles have a diameter in a range of about 30 nm to about 150 nm. 
     
     
         13 . The NO-releasing mesoporous silica particles of  claim 9 , wherein the NO-releasing mesoporous silica particles comprise pores and an interior surface of the pores comprises a diazeniumdiolate-functional group. 
     
     
         14 . The NO-releasing mesoporous silica particles of  claim 13 , wherein the pores have a pore size in a range of 2 to 10 nm. 
     
     
         15 . The NO-releasing mesoporous silica particles of  claim 9 , wherein the NO-releasing mesoporous silica particles are charged with NO at a concentration of at least about 0.4 μmol/mg and release NO with a half-life for release of the NO that is no less than about 2 minutes. 
     
     
         16 . The NO-releasing mesoporous silica particles of  claim 9 , wherein the NO-releasing mesoporous silica particles are made by a process that comprises generating a mesoporous silica particle by reacting tetraethylorthosilicate with a cetyltrimethylammonium halide to generate a cetyltrimethylammonium ion; and exchanging via an ion exchange reaction the cetyltrimethylammonium ion for an organosilane molecule. 
     
     
         17 . The NO-releasing mesoporous silica particles of  claim 16 , wherein the organosilane 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 . 
       
     
     
         18 . The NO-releasing mesoporous silica particles of  claim 17 , wherein the organosilane is one or more of:
 aminosilane N-(2-aminoethyl)-3-aminopropyltrimethoxysilane,   N-(6-aminohexyl)aminopropyl trimethoxysilane,   (3-Aminopropyl)triethoxysilane,   N-methylaminopropyltrimethoxysilane,   and   (3-trimethoxysilyl-propyl)diethylenetriamine or combinations thereof.   
     
     
         19 . The NO-releasing mesoporous silica particles of  claim 9 , wherein said NO-releasing mesoporous silica particles have a half-life for release of the NO that is no less than about 10 minutes. 
     
     
         20 . The NO-releasing mesoporous silica particles of  claim 9 , wherein said NO-releasing mesoporous silica particles have a half-life for release of the NO that is no less than about 25 minutes.