IP Library Granted Patent US 8,889,430
Granted Patent B2
US 8,889,430 · App. 12/299,079 · Granted Nov 18, 2014

Nanostructures, methods of synthesizing thereof, and methods of use thereof

Inventors: Lily Yang (Decatur, GA); Hui Mao (Alpharetta, GA); Shuming Nie (Atlanta, GA); Xiaohu Gao (Shoreline, WA)
Assignee: Emory University
C07K16/2863A61K49/1866A61K49/0032A61K49/0093A61K49/0056A61K49/0058B82Y5/00A61K2039/505A61K49/0034C07K2317/622C07K2317/77
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Quick Facts
Patent No.
US 8,889,430
App. No.
12/299,079
Granted
Nov 18, 2014
Kind
B2
Abstract

A nanostructure and methods of synthesizing same. In one embodiment, the nanostructure includes a magnetic iron oxide nanoparticle, a hydrophobic protection structure including at least an amphiphilic copolymer, wherein the hydrophobic protection structure encapsulates the magnetic iron oxide nanoparticle, and at least one amino-terminal fragment (ATF) peptide or epidermal growth factor receptor (EGFR) antibody conjugated to the amphiphilic copolymer.

Claims (37)

1. A nanostructure, comprising:

a. a magnetic iron oxide nanoparticle;

b. a hydrophobic protection structure including at least an amphiphilic copolymer, wherein the hydrophobic protection structure at least partially encapsulates the magnetic iron oxide nanoparticle; and

c. at least one epidermal growth factor receptor (EGFR) antibody conjugated to the hydrophobic protection structure.

2. The nanostructure of claim 1 , wherein the at least one EGFR antibody is labeled with a fluorescence dye.

3. The nanostructure of claim 2 , wherein the fluorescence dye is a Cy5.5 or an ICG.

4. The nanostructure of claim 1 , wherein the at least one EGFR antibody is a single chain antibody to the epidermal growth factor receptor (ScFvEGFR).

5. The nanostructure of claim 1 , being capable of targeting to tumor cells expressing EGFR.

6. The nanostructure of claim 1 , wherein the amphiphilic copolymer comprises an amphiphilic block copolymer, an amphiphilic random copolymer, an amphiphilic alternating copolymer, an amphiphilic periodic copolymer, or any combination thereof.

7. The nanostructure of claim 6 , wherein the amphiphilic copolymer comprises an amphiphilic block copolymer selected from the group consisting of an amphiphilic diblock copolymer, a triblock copolymer, or any combination thereof.

8. The nanostructure of claim 7 , wherein the amphiphilic block copolymer includes an ABC triblock structure having one or more grafted 8-carbon alkyl side chains.

9. The nanostructure of claim 8 , wherein the ABC triblock structure includes a poly-butylacrylate segment, a poly-ethylacrylate segment, and a poly-methacrylic acid segment.

10. The nanostructure of claim 1 , wherein the amphiphilic copolymer has a molecular weight of about 10,000 to 200,000.

11. The nanostructure of claim 1 , wherein the magnetic iron oxide nanoparticle has a core size of about 1-50 nm.

12. The nanostructure of claim 1 , further comprising a probe disposed on the hydrophobic protection structure, wherein the probe comprises an antibody, a polypeptide, a polynucleotide, a drug molecule, an inhibitor compound, or any combination thereof.

13. A pharmaceutical composition comprising the nanostructure of claim 1 .

14. The pharmaceutical composition of claim 13 , further comprising a probe releasably attached onto the nanostructure, wherein the probe comprises an antibody, a polypeptide, a polynucleotide, a drug molecule, an inhibitor compound, or any combination thereof.

15. A method for target imaging and/or therapy, comprising:

introducing the nanostructure of claim 1 into a subject; and

determining the presence of the target in the subject by detecting the nanostructure.

16. The method of claim 15 , wherein the at least one EGFR antibody is labeled with a fluorescence dye.

17. The method of claim 15 , wherein the nanostructure is visible in magnetic resonance imaging (MRI).

18. The method of claim 15 , wherein the magnetic iron oxide nanoparticle has a core size of about 1-50 nm.

19. The method of claim 15 , wherein the nanostructure further comprises a probe deposed on or encapsulated in the hydrophobic protection structure, and wherein the probe comprises an antibody, a polypeptide, a polynucleotide, a drug molecule, an inhibitor compound, or any combination thereof.

20. The method of claim 15 , wherein the target is tumor cells expressing EGFR.

21. The method of claim 20 , wherein the tumor cells is at least one of pancreatic cancer cells or breast cancer cells.

22. The method of claim 15 , wherein the introducing step is performed by a subcutaneous injection or a systemic injection.

23. The method of claim 22 , wherein when the introducing step is performed by a systemic injection, a plurality of the nanostructure is accumulated substantially in the target region of the subject.

24. The method of claim 15 , wherein the determining step is performed in vivo.

25. The method of claim 15 , wherein determining comprises acquiring an image of the target.

26. The method of claim 15 , wherein the determining step includes a passive targeting process or an active targeting process.

27. The method

of claim 15 , wherein introducing the nanostructure into the subject causes selective accumulation of the nanostructure in a target region of the subject.

28. The method of claim 15 , wherein determining the presence of the target in the subject comprises:

acquiring at least one image of the target; and

determining the presence of the target in the subject from the acquired at least one image of the target.

29. The method of claim 28 , wherein acquiring at least one image of the target comprises acquiring at least one of an MRI image and a florescence image.

Assignments (2)
CONFIRMATORY LICENSE Recorded Dec 1, 2014
From: EMORY UNIVERSITY
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 034498/0185 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 29, 2009
From: YANG, LILY; MAO, HUI; NIE, SHUMING; GAO, XIAOHU
To: EMORY UNIVERSITY
Reel/Frame 022175/0801 →
Continuity (2)
Provisional Application 60797613 · May 4, 2006
Related Publication 20090196831A1 · Aug 6, 2009