Silica-based mesoporous carrier and delivery method of using the same

Abstract

Mesoporous carriers for delivering targets into a cell are provided. The mesoporous carriers comprise hollow silica nanospheres (HSN) or mesoporous silica nanoparticles (MSN) and the targets bound to or encapsulated by the hollow silica nanospheres or the mesoporous silica nanoparticles. The targets includes at least two different targets, and the targets may include peptides, proteins, enzymes and/or enzymatic mimetics.

What is claimed is: 
     
         1 . Mesoporous carriers, for delivering targets into a cell, comprising:
 hollow silica nanospheres (HSN) or mesoporous silica nanoparticles (MSN); and the targets carried by the hollow silica nanospheres or the mesoporous silica nanoparticles, wherein the targets at least includes first targets and second targets, and the first and second targets are different.   
     
     
         2 . The carriers of  claim 1 , wherein the mesoporous silica nanoparticles are surface-functionalized mesoporous silica nanoparticles functionalized with 3-aminopropyl-trimethoxysilane (APTMS). 
     
     
         3 . The carriers of  claim 2 , wherein the surface-functionalized mesoporous silica nanoparticles are bound with crosslinkers containing polyethylene glycol. 
     
     
         4 . The carriers of  claim 3 , wherein the first target is an antibody and the second target is a peptide respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         5 . The carriers of  claim 4 , wherein the antibody is specific to transcriptional factors, mediators or complex in a signalling pathway and the peptide is a nucleus localization sequence (NLS)-peptide or a NLS like-peptide, so that the surface-functionalized mesoporous silica nanoparticles are sequestered outside of a nuclear membrane of the cell. 
     
     
         6 . The carriers of  claim 4 , wherein the antibody is NF-κB p65 antibody and the peptide is TAT transducing peptide. 
     
     
         7 . The carriers of  claim 2 , wherein the first target is superoxide dismutase and the second target is glutathione peroxidase respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         8 . The carriers of  claim 7 , wherein the first target is TAT transducing peptide bound superoxide dismutase and the second target is TAT transducing peptide bound glutathione peroxidase respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         9 . The carriers of  claim 7 , wherein at least one of superoxide dismutase and glutathione peroxidase is bound to the mesoporous silica nanoparticles in a denatured form or a partially active form. 
     
     
         10 . The carriers of  claim 2 , wherein the surface-functionalized mesoporous silica nanoparticles are labelled with a tracking agent or a dye. 
     
     
         11 . The carriers of  claim 10 , wherein the dye is fluorescein isothiocyanate. 
     
     
         12 . The carriers of  claim 1 , wherein the first and second targets are different enzymes or catalytic mimetics capable of catalysing a cascade reaction. 
     
     
         13 . The carriers of  claim 12 , wherein the enzymes or catalytic mimetics are capable of catalysing the cascade reaction involved in scavenges free radicles in the cell, so as to protect the cell against ROS induced stress. 
     
     
         14 . The carriers of  claim 1 , wherein at least one of the first and second targets is bound to the mesoporous silica nanoparticles in a denatured form or a partially active form. 
     
     
         15 . The carriers of  claim 1 , wherein the first and second targets are co-encapsulated within the hollow silica nanospheres. 
     
     
         16 . The carriers of  claim 15 , wherein the first and second targets are different enzymes or catalytic mimetics capable of catalysing a cascade reaction. 
     
     
         17 . The carriers of  claim 16 , wherein the enzymes or catalytic mimetics are capable of catalysing the cascade reaction involved in scavenges free radicles in the cell, so as to protect the cell against ROS induced stress. 
     
     
         18 . The carriers of  claim 15 , the first target is polyethyleneimine-grafted superoxide dismutase and the second target is polyethyleneimine-grafted catalase. 
     
     
         19 . A method of delivering targets into a cell, comprising:
 providing mesoporous carriers, wherein the mesoporous carriers comprises hollow silica nanospheres (HSN) or mesoporous silica nanoparticles (MSN) and the targets carried by the hollow silica nanospheres or the mesoporous silica nanoparticles, and the targets at least include first targets and second targets, and the first and second targets are different;   contacting the mesoporous carriers with the cell by incubating the cell with the mesoporous carriers; and   delivering the first targets and the second targets into the cell at the same time, wherein the mesoporous carriers and the targets carried by the hollow silica nanospheres or the mesoporous silica nanoparticles enter into the cell.   
     
     
         20 . The method of  claim 19 , wherein providing mesoporous carriers includes surface-functionalizing the mesoporous silica nanoparticles with 3-aminopropyl-trimethoxysilane (APTMS) to form surface-functionalized mesoporous silica nanoparticles. 
     
     
         21 . The method of  claim 20 , wherein the surface-functionalized mesoporous silica nanoparticles are bound with crosslinkers containing polyethylene glycol. 
     
     
         22 . The method of  claim 21 , wherein the first target is an antibody and the second target is a peptide respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         23 . The method of  claim 22 , wherein the antibody is specific to transcriptional factors, mediators or complex in a signalling pathway and the peptide is a nucleus localization sequence (NLS)-peptide or a NLS like-peptide, so that the surface-functionalized mesoporous silica nanoparticles entering into the cell are sequestered outside of a nuclear membrane of the cell. 
     
     
         24 . The method of  claim 22 , wherein the antibody is NF-κB p65 antibody and the peptide is TAT transducing peptide. 
     
     
         25 . The method of  claim 20 , wherein the first target is superoxide dismutase and the second target is glutathione peroxidase respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         26 . The method of  claim 25 , wherein the first target is TAT transducing peptide bound superoxide dismutase and the second target is TAT transducing peptide bound glutathione peroxidase respectively bound to the crosslinkers on surface-functionalized mesoporous silica nanoparticles. 
     
     
         27 . The method of  claim 25 , wherein at least one of superoxide dismutase and glutathione peroxidase is bound to the mesoporous silica nanoparticles in a denatured farm or a partially active form. 
     
     
         28 . The method of  claim 20 , wherein the surface-functionalized mesoporous silica nanoparticles are labelled with a tracking agent or a dye. 
     
     
         29 . The method of  claim 28 , wherein the dye is fluorescein isothiocyanate. 
     
     
         30 . The method of  claim 19 , wherein the first and second targets are different enzymes or catalytic mimetics capable of catalysing a cascade reaction. 
     
     
         31 . The method of  claim 30 , wherein the enzymes or catalytic mimetics are capable of catalysing the cascade reaction involved in scavenges free radicles in the cell, so as to protect the cell against ROS induced stress. 
     
     
         32 . The method of  claim 19 , wherein at least one of the first and second targets is bound to the mesoporous silica nanoparticles in a denatured form or a partially active form. 
     
     
         33 . The method of  claim 19 , wherein the first and second targets are co-encapsulated within the hollow silica nanospheres. 
     
     
         34 . The method of  claim 33 , wherein the first and second targets are different enzymes or catalytic mimetics capable of catalysing a cascade reaction. 
     
     
         35 . The method of  claim 34 , wherein the enzymes or catalytic mimetics are capable of catalysing the cascade reaction involved in scavenges free radicles in the cell, so as to protect the cell against ROS induced stress. 
     
     
         36 . The method of  claim 34 , the first target is polyethyleneimine-grafted superoxide dismutase and the second target is polyethyleneimine-grafted catalase.