Polyarginine-coated magnetic nanovector and methods of use thereof

Abstract

Polyarginine-coated nanoparticle, and methods for making and using the nanoparticle. The nanoparticle can have a core that includes a material that imparts magnetic resonance imaging activity to the particle and, optionally, include one or more of an associated therapeutic agent, targeting agent, and diagnostic agent.

1 . A nanoparticle, comprising:
 (a) a core having a surface and comprising a core material; and   (b) a polyarginine coating covalently coupled to the surface of the core.   
     
     
         2 . The nanoparticle of  claim 1  further comprising a therapeutic agent. 
     
     
         3 . The nanoparticle of  claim 1  further comprising a targeting agent. 
     
     
         4 . The nanoparticle of  claim 1  further comprising a therapeutic agent and a targeting agent. 
     
     
         5 . The nanoparticle of  claim 1 , wherein the polyarginine has an average molecular weight from about 2,000 to about 200,000 g/mole. 
     
     
         6 . The nanoparticle of  claim 2 , wherein the therapeutic agent is selected from the group consisting of a small organic molecule, a peptide, an aptamer, a protein, and a nucleic acid. 
     
     
         7 . The nanoparticle of  claim 2 , wherein the therapeutic agent is an RNA or a DNA. 
     
     
         8 . The nanoparticle of  claim 2 , wherein the therapeutic agent is an siRNA. 
     
     
         9 . The nanoparticle of  claim 2 , wherein the therapeutic agent is covalently coupled to the nanoparticle through a cleavable linkage. 
     
     
         10 . The nanoparticle of  claim 3 , wherein the targeting agent is selected from the group consisting of a small organic molecule, a peptide, an aptamer, a protein, and a nucleic acid. 
     
     
         11 . The nanoparticle of  claim 3 , wherein the targeting agent is selected from the group consisting of a chlorotoxin, folic acid, methotrexate, RGD, VHPNKK, A10 RNA aptamer, transferrin, and herceptin. 
     
     
         12 . The nanoparticle of  claim 1 , wherein the core material comprises a material having magnetic resonance imaging activity. 
     
     
         13 . The nanoparticle of  claim 1  further comprising a poly(alkylene oxide) oligomer intermediate the core and the polyarginine coating. 
     
     
         14 . The nanoparticle of  claim 1 , wherein the poly(alkylene oxide) oligomer is covalently coupled to the core by siloxane linkages. 
     
     
         15 . The nanoparticle of  claim 2  further comprising a fluorescent agent. 
     
     
         16 . The nanoparticle of  claim 3  further comprising a fluorescent agent. 
     
     
         17 . The nanoparticle of  claim 4  further comprising a fluorescent agent. 
     
     
         18 . The nanoparticle of  claim 1  further comprising a fluorescent agent. 
     
     
         19 . A composition, comprising a nanoparticle of  claim 1  and a carrier suitable for administration to a warm-blooded subject. 
     
     
         20 - 24 . (canceled) 
     
     
         25 . A method for introducing a nanovector into a cell via transcytosis, comprising contacting a cell with a nanoparticle of  claim 1 . 
     
     
         26 . A method for silencing or reducing the expression level of a gene, comprising contacting a cell of interest with a nanoparticle of  claim 1 , wherein the nanoparticle comprises a vector effective to silence or reduce the expression level of the gene. 
     
     
         27 . A method for detecting cells or tissues by magnetic resonance imaging, comprising:
 (a) contacting cells or tissues of interest with a nanoparticle of  claim 1 ; and   (b) measuring the level of binding of the nanoparticle, wherein an elevated level of binding, relative to normal cells or tissues, is indicative of binding to the cells or tissues of interest.   
     
     
         28 . A method for treating a tissue, comprising contacting a tissue of interest with a nanoparticle of  claim 1 .