IMPRINTED POLYMER NANOPARTICLES

• US 20120097613A1
• Filed: 01/11/2010
• Published: 04/26/2012
• Est. Priority Date: 01/12/2009
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Shea, Kenneth J., Hoshino, Yu
• Granted Patent: US 9,173,943 B2
• Time in Patent Office: Days
• US Class Current: 210/660
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 47/36 Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 9/5138 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5192 Processes
• CPC Class Codes: B01D 15/3852 using imprinted phases or molecular recognition; using imprinted phases
• CPC Class Codes: B01J 20/261 obtained by reactions only involving carbon to carbon unsaturated bonds macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds per se C08F
• CPC Class Codes: B01J 20/267 Cross-linked polymers
• CPC Class Codes: B01J 20/268 Polymers created by use of a template, e.g. molecularly imprinted polymers
• CPC Class Codes: B01J 20/28007 with size in the range 1-100 nanometers, e.g. nanosized particles, nanofibers, nanotubes, nanowires or the like carbon nanostructures B01J20/205
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: C07K 1/22 Affinity chromatography or related techniques based upon selective absorption processes
• CPC Class Codes: C08F 2/10 Aqueous solvent
• CPC Class Codes: C08F 2/44 Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
• CPC Class Codes: G01N 2600/00 Assays involving molecular imprinted polymers/polymers created around a molecular template
• CPC Class Codes: G01N 33/5432 Liposomes or microcapsules
• CPC Class Codes: G01N 33/54346 Nanoparticles

Abstract

The present invention relates to imprinted polymer nanoparticles. In particular, the present invention provides imprinted polymer nanopaticles polymerized in the presence of a target molecule (e.g., peptide), wherein the imprinted polymer nanoparticles comprise vinyl, acryl, and/or methacryl monomers, wherein the monomers have affinity for the target molecule. The present invention also relates to methods of using imprinted polymer nanoparticles in biomoacromolecular purification methods (e.g., to purify monoclonal antibodies or hormones), in toxin elimination methods (e.g., hemoperfusion), in diagnostics, in research, as well as in therapeutic methods (e.g., therapeutic methods where antisera or monoclonal antibodies are normally employed).

Claims

1. A composition comprising imprinted polymer nanoparticles that are specific for a target molecule, wherein said imprinted polymer nanoparticle comprise vinyl, acryl, and/or methacryl monomers, and wherein said monomers have affinity for said target molecule.

2. The composition of claim 1, wherein said imprinted polymer nanoparticles result from polymerization of said monomers in the presence of said target molecule.

3. The composition of claim 1, wherein said composition further comprises said target molecule.

4. The composition of claim 1, wherein 30-50% of said imprinted polymer nanoparticle is either said vinyl monomers, or said acryl monomers, or said methacryl monomers.

5. The composition of claim 1, wherein 0-10% of said imprinted polymer nanoparticle is either said vinyl monomers, or said acryl monomers, or said methacryl monomers.

6. The composition of claim 1, wherein imprinted polymer nanoparticle comprises at least two of said monomers, wherein said at least two monomers are selected from:

N-t-butylacrylamide (TBAm), acrylic acid (AAc), N-isopropylacrylamide (NIPAm), N,N′

-methylenebis(acrylamide) (MBAm), N,N′

-ethylenebis(acrylamide) (EBAm), acrylamide (AAm), 1-vinyl imidazole (VI), N-(3-aminopropyl)acrylamide (APAm), N-phenyl acrylamide (PAm), N-[2-[[[5-(Dimethylamino)-1-naphthalenyl]sulfonyl]-aminolethyl1-2-propenamide (DANSAm), fluorescein o-acrylate (FAc), polyethylene grycol diacrylate (PEGDAc), N-t-butylmethacrylamide (TBMAm), methacrylic acid (MAAc), N-isopropylmethacrylamide (NIPMAm), N,N′

-methylenebis(methacrylamide) (MBMAm), N,N′

-ethylenebis(methacrylamide) (EBMAm), methacrylamide (MAAm), N-(3-aminopropyl)methacrylamide (APMAm), N-phenyl methacrylamide (PMAmN-[2-[[[5-(Dimethylamino)-1-naphthalenyl]sulfonyl]-amino]ethyl]-2-methyl-Z-propenamide (DANSMAm), fluorescein o-methacrylate (FMAc) and polyethylene grycol dimethacrylate (PEGDMAc).

7. The composition of claim 1, wherein said imprinted polymer nanoparticles further comprises a crosslinking agent.

8. The composition of claim 7, wherein said crosslinking agent comprises N,N′

-methylenebis(acrylamide).

9. A method of making imprinted polymer nanoparticles comprising:

a) providing;

i) vinyl, acryl, and/or methacryl monomers,

ii) target molecules, and

iii) an aqueous medium; and

b) combining said monomers and said target molecules in said aqueous medium to generate a reaction mixture; and

c) incubating said reaction mixture under polymerization conditions such that imprinted polymer nanoparticles are generated that are specific for said target molecules.

10. The method of claim 9, wherein 30-50% of said reaction mixture is either said vinyl monomers, or said acryl monomers, or said methacryl monomers.

11. The method of claim 9, wherein 0-10% of said reaction mixture is either said vinyl monomers, or said acryl monomers, or said methacryl monomers.

12. The method of claim 9, wherein said target molecules are proteins.

13. The method of claim 9, wherein said target molecules are toxins.

14. The method of claim 9, wherein said target molecules are polysaccharides.

15. The method of claim 9, wherein said reaction mixture further comprises an ionic surfactant.

16. The method of claim 15, wherein said ionic surfactant comprises sodium dodecyl sulfate.

17. The method of claim 9, wherein said reaction mixture further comprises a crosslinking agent.

18. The method of claim 17, wherein said crosslinking agent comprises N,N′

-methylenebis(acrylamide).

19. The method of claim 9, wherein said reaction mixture further comprises acrylamide.

20. A method of purifying target molecules from an initial sample, comprising:

a) providing;

i) an initial sample comprising target molecules and contaminating molecules, and

ii) imprinted polymer nanoparticles that are specific for said target molecules, wherein said imprinted polymer nanoparticle comprise vinyl, acryl, and/or methacryl monomers, wherein said monomers have affinity for said target molecules; and

b) contacting said initial sample with said imprinted polymer nanoparticles under conditions such that at least a portion of said contaminating molecules are removed from said initial sample thereby generating a purified target molecule sample.