US2012207795A1PendingUtilityA1

Cationic polymer coated mesoporous silica nanoparticles and uses thereof

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Individually held — no corporate assignee on recordPriority: Jul 13, 2010Filed: Mar 23, 2012Published: Aug 16, 2012
Est. expiryJul 13, 2030(~4 yrs left)· nominal 20-yr term from priority
Inventors:Jeffrey I. ZinkAndre E. NelTian XiaZhaoxia JiHuan MengZongxi LiMonty LiongMin XueDerrick Y. Tarn
A61P 35/00A61K 31/713A61K 9/5192A61K 9/5115Y10T428/2982A61K 9/0019B82Y 5/00A61K 9/5146A61K 31/704
43
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Claims

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.

Claims

exact text as granted — not AI-modified
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 cationic therapeutic compound and an 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 . The submicron structure of  claim 2 , wherein the siRNA reduces translation of a protein that causes resistance to said therapeutic compound in the cell. 
     
     
         4 . The submicron structure of  claim 2 , wherein the siRNA reduces translation of p-glycoprotein. 
     
     
         5 . The submicron structure of  claim 2 , wherein the cationic 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 . The submicron structure of  claim 1 , wherein the cationic polymer is polyethyleneimine. 
     
     
         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. 
     
     
         13 . The submicron structure of  claim 11 , wherein the oligonucleotide is RNA. 
     
     
         14 . The submicron structure of  claim 13 , wherein the RNA is siRNA. 
     
     
         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. 
     
     
         17 . The submicron structure of  claim 15 , wherein the therapeutic compound is cationic. 
     
     
         18 . The submicron structure of  claim 15 , wherein the therapeutic compound is anionic. 
     
     
         19 . The submicron structure of  claim 1 , wherein the silica body is mesoporous. 
     
     
         20 . The submicron structure of  claim 1 , wherein the pores are substantially cylindrical pores having an ensemble average diameter between about 1 nm and about 10 nm. 
     
     
         21 . The submicron structure of  claim 1 , wherein the silica body is substantially spherical having a diameter between about 50 nm and about 1000 nm. 
     
     
         22 . The submicron structure of  claim 1 , wherein the silica body is substantially spherical having a diameter between about 100 nm and about 500 nm. 
     
     
         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 . The submicron structure of  claim 23 , wherein the silica body is substantially spherical having a diameter less than 100 nm. 
     
     
         25 . The submicron structure of  claim 1 , further comprising a plurality of anionic molecules attached to an outer surface of said silica body. 
     
     
         26 . A submicron structure according to  claim 25 , wherein said plurality of anionic molecules comprise a phosphonate moiety. 
     
     
         27 . A submicron structure according to  claim 25 , wherein said plurality of anionic molecules are trihydroxysilylpropyl methylphosphonate. 
     
     
         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 . The submicron structure according to  claim 1 , further comprising a light-emitting compound covalently bonded to the surface of the silica body. 
     
     
         30 . The submicron structure of  claim 1  further comprising a core structure within said silica body. 
     
     
         31 . The submicron structure of  claim 30 , wherein said core structure is a superparamagnetic nanocrystal, silver nanocrystal, or gold nanocrystal. 
     
     
         32 . The submicron structure of  claim 31 , wherein the superparamagnetic nanocrystal is an iron oxide nanocrystal. 
     
     
         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 . The submicron structure of  claim 33 , further comprising a therapeutic compound. 
     
     
         35 . The submicron structure of  claim 33 , further comprising a cationic polymer on the surface of said silica body. 
     
     
         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 . A therapeutic method comprising administering to a subject in need of treatment an effective amount of a submicron structure according to  claim 33 . 
     
     
         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 . The method of  claim 37  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. 
     
     
         39 . A method for transfecting a cell comprising administering to the cell a submicron structure according to  claim 1  comprising an oligonucleotide. 
     
     
         40 . A method for transfecting a cell comprising administering to the cell a submicron structure according to  claim 33  comprising an oligonucleotide.

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