Polyarginine-coated magnetic nanovector and methods of use thereof

Patent metadata

Field	Value
Publication number	US-11307197-B2
Application number	US-201615012617-A
Country	US
Kind code	B2
Filing date	Feb 1, 2016
Priority date	May 11, 2012
Publication date	Apr 19, 2022
Grant date	Apr 19, 2022

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 silencing or reducing the expression level of a gene, comprising contacting a cancer cell of interest with a nanovector effective to silence or reduce the expression level of the gene, which comprises a nanoparticle and a therapeutic agent, wherein the nanoparticle comprises:
(a) a core consisting of a core material and a core surface, wherein the core material is a material having magnetic resonance imaging activity;
(b) a polyarginine coating covalently coupled to the core surface; and
(c) a poly(alkylene oxide) oligomer intermediate the core surface and the polyarginine coating, to which the polyarginine coating is covalently bonded.

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

3. The method of claim 2 , 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.

4. The method claim 2 , wherein the nanoparticle further comprises a fluorescent agent, which is covalently attached to the nanoparticle.

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

6. The method of claim 1 , 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 1 , wherein the therapeutic agent is an RNA or a DNA.

8. The method of claim 1 , wherein the therapeutic agent is an siRNA.

9. The method of claim 1 , wherein the poly(alkylene oxide) oligomer is covalently coupled to the core surface by siloxane linkages.

10. The method of claim 1 , wherein the nanoparticle further comprises a fluorescent agent, which is covalently attached to the nanoparticle.

11. The method of claim 1 , wherein the nanoparticle is introduced into the cancer cell via transcytosis.

12. A method for silencing or reducing the expression level of a gene, comprising contacting a cancer cell of interest with a nanovector effective to silence or reduce the expression level of the gene, which comprises a nanoparticle and a therapeutic agent, wherein the nanoparticle comprises:
(a) a core consisting of a core material and a core surface;
(b) a polyarginine coating covalently coupled to the core surface; and
(c) a poly(alkylene oxide) oligomer intermediate the core surface and the polyarginine coating, to which the polyarginine coating is covalently bonded; and
(d) a fluorescent agent covalently attached to the nanoparticle.

13. A method for silencing or reducing the expression level of a gene, comprising contacting a cancer cell of interest with a nanovector effective to silence or reduce the expression level of the gene, which comprises a nanoparticle and a therapeutic agent, wherein the nanoparticle comprises:
(a) a core consisting of a core material and a core surface;
(b) a polyarginine coating covalently coupled to the core surface;
(c) a poly(alkylene oxide) oligomer intermediate the core surface and the polyarginine coating, to which the polyarginine coating is covalently bonded;
(d) a fluorescent agent covalently attached to the nanoparticle; and
(e) a targeting agent.

Assignees

• Univ Washington Through Its Center For Commercialization
• Univ Washington

Inventors

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

Classifications

• A61K49/186 Primary

  the organic macromolecular compound being polyethyleneglycol [PEG] · 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

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title

• C12N15/85

  for animal cells · CPC title