Polyarginine-coated magnetic nanovector and methods of use thereof

Patent metadata

Field	Value
Publication number	US-2016153976-A1
Application number	US-201615012617-A
Country	US
Kind code	A1
Filing date	Feb 1, 2016
Priority date	May 11, 2012
Publication date	Jun 2, 2016
Grant date	—

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.

First claim

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows:

1 . A method for introducing a nanovector into a cell via transcytosis, comprising contacting a cell with 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 method of claim 1 , wherein the nanoparticle of claim 1 further comprises a therapeutic agent.

3 . The method of claim 1 , wherein the nanoparticle further comprises a targeting agent.

4 . The method of claim 1 , wherein the nanoparticle further comprises a therapeutic agent and a targeting agent.

5 . The method of claim 1 , wherein the polyarginine has an average molecular weight from about 2,000 to about 200,000 g/mole.

6 . The method 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 method of claim 2 , wherein the therapeutic agent is an RNA or a DNA.

8 . The method of claim 2 , wherein the therapeutic agent is an siRNA.

9 . The method 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.

10 . The method of claim 1 , wherein the core material comprises a material having magnetic resonance imaging activity.

11 . The method of claim 1 , wherein the nanoparticle further comprises a poly(alkylene oxide) oligomer intermediate the core and the polyarginine coating.

12 . The method of claim 11 , wherein the poly(alkylene oxide) oligomer is covalently coupled to the core by siloxane linkages.

13 . The method of claim 1 , wherein the nanoparticle further comprises a fluorescent agent.

14 . The method of claim 2 , wherein the nanoparticle further comprises a fluorescent agent.

15 . The method of claim 3 , wherein the nanoparticle further comprises a fluorescent agent.

16 . The method of claim 4 , wherein the nanoparticle further comprises a fluorescent agent.

17 . A method for silencing or reducing the expression level of a gene, comprising contacting a cell of interest with a nanoparticle comprising a vector effective to silence or reduce the expression level of the gene, wherein the nanoparticle comprises:
(a) a core having a surface and comprising a core material; and (b) a polyarginine coating covalently coupled to the surface of the core.

18 . A method for detecting cells or tissues by magnetic resonance imaging, comprising:
(a) contacting cells or tissues of interest with a nanoparticle, wherein the nanoparticle comprises:
(i) a core having a surface and comprising a core material; and
(ii) a polyarginine coating covalently coupled to the surface of the core; 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.

Assignees

• Univ Washington Ct Commerciali

Inventors

• Zhang Miqin
• Veiseh Omid
• Fang Chen
• Kievit Forrest

Classifications

• A61K49/186 Primary

  the organic macromolecular compound being polyethyleneglycol [PEG] · CPC title

• C12N2310/14

  interfering nucleic acids [NA] · CPC title

• G01N33/582

  with fluorescent label · CPC title

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• G01N33/54346 Primary

  Nanoparticles · CPC title