DNA-functionalized scaffolds for drug capture applications

Patent metadata

Field	Value
Publication number	US-10646505-B2
Application number	US-201715696474-A
Country	US
Kind code	B2
Filing date	Sep 6, 2017
Priority date	Sep 7, 2016
Publication date	May 12, 2020
Grant date	May 12, 2020

Abstract

This disclosure is directed to structured compositions, including DNA-functionalized scaffolds, for drug capture, and methods and devices for sequestering chemotherapeutics from physiological fluids using the functionalized scaffolds.

First claim

What is claimed:

1. A structured composition comprising DNA operatively linked to a scaffold through an organic polymer surface and/or a hydroxylated inorganic surface of the scaffold, wherein the DNA is operatively linked to the organic polymer surface or hydroxylated inorganic surface by attachment to a linking group, wherein:
(a) the organic polymer surface comprises a lithographically patterned organic polymer; or
(b) the scaffold comprises a three-dimensionally (3D) photopolymerized patterned polymer structure; or
(c) the linking group is covalently bound to the organic polymer surface, the covalent bond resulting from the co-polymerization of an unsaturated moiety of a linker group precursor with a prepolymer of the organic polymer to form the linking group pendant to the surface; or
(d) the organic polymer surface comprises a polyhydroxylated organic polymer comprising (co)polymerized polyvinyl alcohol, polyalkylhydroxy(meth)acrylate, polyhydroxyalkyl(meth)acrylamide, monoglycerol(meth)acrylate, monoglycerol(meth)acrylamide, or a combination thereof, or (co)polymerized (meth)acrylate linkages; or
(e) the linking group is covalently bound to the hydroxylated inorganic surface.

2. The structured composition of claim 1 , where the scaffold is in the form of a sheet, tube, microparticle, macroparticle, nanoparticle, nanotube, nanofiber, microfiber, fiber, wire, membrane, mesh, or web.

3. The structured composition of claim 2 , wherein the structured composition is contained in or on a medical device.

4. The structured composition of claim 3 , wherein the structured composition is in a form of a structured fiber, wire, mesh, or membrane.

5. The structured composition of claim 4 , wherein the structured composition is incorporated into a catheter, stent, cannula, or like flexible tubular device capable of being delivered locally to a position within the vascular system of a stent.

6. The structured composition of claim 5 , wherein the structured composition is alternatively extendible from and retractable into the catheter, stent, cannula, or like flexible tubular device.

7. The structured composition of claim 5 , wherein the exterior surface of the catheter, stent, cannula, or like flexible tubular device is coated with the structured composition.

8. The structured composition of claim 1 , wherein the linking group comprises one or more internal covalent aliphatic or aromatic amide, amine, ester, ether, thioamide, thioester, or thioether bonds, or a coordinative ligand linkage to a transition metal.

9. The structured composition of claim 1 , wherein the DNA is genomic DNA.

10. The structured composition of claim 1 , wherein the DNA is linked to the linking group by:
(a) a covalent aliphatic or aromatic amide, amine, ester, ether, thioamide, thioester, or thioether bond; or
(b) intercalation or an electrostatic, pi-pi, and/or hydrogen-bonding mechanisms with a moiety on the linking group; or
(c) bonding to a cis-platin-like moiety covalently attached to the linking group.

11. The structured composition of claim 1 , wherein the scaffold and/or the organic or hydroxylated inorganic surface comprises the organic polymer surface comprising the polyhydroxylated organic polymer comprising (co)polymerized (meth)acrylate linkages.

12. The structured composition of claim 1 , wherein the scaffold and/or the organic polymer surface or hydroxylated inorganic surface comprises the lithographically patterned organic polymer.

13. The structured composition of claim 1 , wherein the scaffold comprises the three-dimensionally (3D) photopolymerized patterned polymer structure.

14. The structured composition of claim 1 , wherein the scaffold and/or the organic polymer surface or hydroxylated inorganic surface comprises the organic polymer and the linking group is covalently bound to the organic polymer surface, the covalent bond resulting from the co-polymerization of an unsaturated moiety of a linker group precursor with a prepolymer of the organic polymer to form the linking group pendant to the surface.

15. The structured composition of claim 1 , wherein the linking group is covalently bound to the organic surface comprising the polyhydroxylated organic polymer.

16. The structured composition of claim 1 , wherein the linking group is covalently bound to the organic polymer surface by an aliphatic or aromatic amide, amine, ester, ether, thioamide, thioester, thioether or silyl ether linkage.

17. The structured composition of claim 1 , wherein the scaffold and/or the organic polymer surface or hydroxylated inorganic surface comprises the polyhydroxylated organic polymer comprises (co)polymerized polyvinyl alcohol, polyalkylhydroxy(meth)acrylate, polyhydroxyalkyl(meth)acrylamide, monoglycerol(meth)acrylate, monoglycerol(meth)acrylamide, or a combination thereof.

18. The structured composition of claim 1 , wherein the scaffold and/or the organic polymer surface or hydroxylated inorganic surface comprises the organic polymer surface comprising the polyhydroxylated organic polymer comprising (co)polymerized 2 hydroxyethyl(meth)acrylate, 2-hydroxypropyl(meth)acrylate, 3-hydroxypropyl(meth)acrylate, 2-hydroxybutyl(meth)acrylate, 3-hydroxybutyl(meth)acrylate, and 4-hydroxybutyl(meth)acrylate, and glycerol mono(meth)acrylate.

19. The structured composition of claim 1 , wherein the scaffold and the organic polymer surface or hydroxylated inorganic surface comprises a hydroxylated metal or hydroxylated metalloid.

20. The structured composition of claim 1 , wherein the scaffold and the organic polymer surface or hydroxylated inorganic surface comprises a hydroxylated metal oxide or hydroxylated metalloid oxide.

21. The structured composition of claim 20 , wherein the linking group is covalently bound to the hydroxylated inorganic surface.

22. The structured composition of claim 21 , wherein the hydroxylated inorganic surface comprises a hydrous oxide of Al, B, Ca, Cr, Fe, Mg, Ni, Si, Sn, Ti, Zn, or Zr.

23. The structured composition of claim 21 , wherein the hydroxylated inorganic surface comprises a hydroxylated silicate glass or clay.

24. The structured composition of claim 21 , wherein the linker group is covalently attached to the hydroxylated inorganic surface by a metal silyl ether linkage.

25. The structured composition of claim 1 , further comprising a captured drug, wherein the captured drug is bonded or otherwise attached to the DNA.

26. The structured composition of claim 25 , wherein the captured drug comprises doxorubicin (DOX), epirubicin (EPI), daunorubicin, a nitrogen mustard, a nitrosourea, an alkyl sulfonate, a triazine, an ethylenimine, trabectedin, or a Pt-drug.

27. The structured composition of claim 1 , wherein the structured composition is in physical contact with a physiological fluid.

28. The structured composition of claim 27 , wherein the physiological fluid is saline, blood, serum, or blood plasma.

29. A method of removing drugs from a physiological fluid, the method comprising contacting the physiological fluid with a structured composition for a time sufficient to remove at least a portion of the drug from the physiological fluid, wherein the structured composition comprises DNA operatively linked to a scaffold through an organic polymer surface and/or hydroxylated inorganic surface of the scaffold, wherein the DNA is linked to the organic

Assignees

• California Inst Of Techn

Inventors

• Schulz Michael D
• Blumenfeld Carl M
• Grubbs Robert H
• Greer Julia R
• Yee Daryl Wei Liang

Classifications

• A61L29/16

  Biologically active materials, e.g. therapeutic substances {(A61L29/048 takes precedence)} · CPC title

• A61L2300/258

  Genetic materials, DNA, RNA, genes, vectors, e.g. plasmids · CPC title

• A61K31/711 Primary

  Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links · CPC title

• A61L31/10

  Macromolecular materials · CPC title

• C08F293/005

  using free radical "living" or "controlled" polymerisation, e.g. using a complexing agent · CPC title