Cationic polymer coated mesoporous silica nanoparticles and uses thereof

Abstract

A submicron structure having a silica body defining a plurality of pores is described. The submicron body may be spherical or non-spherical, and may include a cationic polymer or co-polymer on the surface of said silica body. The submicron structure may further include an oligonucleotide and be used to deliver the oligonucleotide to a cell. The submicron structure may further include a therapeutic agent and be used to deliver the therapeutic agent to a cell. An oligonucleotide and therapeutic agent may be used together. For example, when the oligonucleotide is an siRNA, the composition may be used to decrease cellular resistance to the therapeutic agent by decreasing translation of a resistance gene.

1 : A submicron structure, comprising:
 a silica body defining a plurality of pores and an outer surface between pore openings of said plurality of pores;   a cationic polymer on the surface of said silica body; and   wherein said submicron structure has a maximum dimension less than one micron.   
     
     
         2 : The submicron structure of  claim 1 , further comprising a therapeutic compound and oligonucleotide electrostatically bound to the cationic polymer wherein the oligonucleotide is an siRNA that reduces translation of a protein causing resistance in a cell. 
     
     
         3 - 4 . (canceled) 
     
     
         5 : The submicron structure of  claim 2 , wherein the therapeutic compound is doxirubicin. 
     
     
         6 : The submicron structure of  claim 1 , wherein the cationic polymer is electrostatically bound to the silica body. 
     
     
         7 : The submicron structure of  claim 1 , wherein the cationic polymer is selected from the group consisting of polyethyleneimine, polyamidoamine, polylysine, poly(allylamine), and poly(diallyldimethylammonium chloride). 
     
     
         8 . (canceled) 
     
     
         9 : The submicron structure of  claim 1 , wherein the cationic polymer is a cationic co-polymer. 
     
     
         10 : The submicron structure of  claim 1 , wherein the cationic co-polymer is a co-polymer of poly(ethyleneimine) and poly(ethylene glycol). 
     
     
         11 : The submicron structure of  claim 1 , comprising an oligonucleotide electrostatically bound to said cationic polymer. 
     
     
         12 : The submicron structure of  claim 11 , wherein the oligonucleotide is DNA, or RNA, or siRNA. 
     
     
         13 - 14 . (canceled) 
     
     
         15 : The submicron structure of  claim 1 , comprising a therapeutic compound within the silica body or pores of the silica body. 
     
     
         16 : The submicron structure of  claim 15 , wherein:
 the therapeutic compound is hydrophobic, or   the therapeutic compound is cationic; or   the therapeutic compound is anionic.   
     
     
         17 - 18 . (canceled) 
     
     
         19 : The submicron structure of  claim 1 , wherein the silica body is mesoporous. 
     
     
         20 - 22 . (canceled) 
     
     
         23 : The submicron structure of  claim 1 , wherein the silica body is substantially spherical having a diameter between about 20 nm and about 200 nm. 
     
     
         24 . (canceled) 
     
     
         25 : The submicron structure of  claim 1 , further comprising a plurality of anionic molecules attached to an outer surface of said silica body. 
     
     
         26 : The submicron structure according to  claim 25 , wherein said plurality of anionic molecules comprise a phosphonate moiety. 
     
     
         27 . (canceled) 
     
     
         28 : The submicron structure according to  claim 1 , further comprising a light-emitting compound, peptide, protein, oligonucleotide, sugar, oligosaccharide, or polysaccharide covalently bonded to the surface of the silica body. 
     
     
         29 - 32 . (canceled) 
     
     
         33 : A submicron structure, comprising:
 a silica body defining a plurality of pores and an outer surface between pore openings of said plurality of pores,   wherein the submicron structure has an aspect ratio greater than 1.3, and   wherein said submicron structure has a maximum dimension less than one micron.   
     
     
         34 - 35 . (canceled) 
     
     
         36 : A therapeutic method comprising administering to a subject in need of treatment an effective amount of a submicron structure according to  claim 1 . 
     
     
         37 . (canceled) 
     
     
         38 : The method of  claim 36  for treating drug resistant cancer wherein the submicron structure comprises an siRNA that reduces translation of a protein causing resistance in the drug resistant cancer. 
     
     
         38 . (canceled) 
     
     
         39 : A method for transfecting a cell comprising administering to the cell a submicron structure according to  claim 1  comprising an oligonucleotide. 
     
     
         40 . (canceled)