Functionalized nanodiamonds as delivery platforms for nucleic acids

Patent metadata

Field	Value
Publication number	US-9359282-B2
Application number	US-201414255001-A
Country	US
Kind code	B2
Filing date	Apr 17, 2014
Priority date	Apr 19, 2013
Publication date	Jun 7, 2016
Grant date	Jun 7, 2016

Abstract

The present application relates to functionalized nanodiamonds, to complexes comprising a functionalized nanodiamond reversibly bound to a nucleic acid and to compositions comprising such functionalized nanodiamonds and complexes. In particular, the functionalized nanodiamonds comprise at least one naturally occurring basic amino acid, or analogs or derivatives thereof, covalently linked to a nanodiamond. The present application also includes methods and uses of the complexes and compositions, for example for delivering a nucleic acid to a cell.

First claim

The invention claimed is:

1. A functionalized nanodiamond comprising at least one naturally occurring basic amino acid, or an analog or derivative of a naturally occurring basic amino acid, or an acid addition salt thereof, covalently linked to a nanodiamond, wherein the at least one naturally occurring basic amino acid, or an analog or derivative of a naturally occurring basic amino acid, or an acid addition salt thereof, is covalently linked to the nanodiamond via an amide linkage, and/or wherein the at least one naturally occurring basic amino acid, or an analog or derivative of a naturally occurring basic amino acid, or an acid addition salt thereof, is covalently linked to the nanodiamond via a linker group comprising a C 1-6 alkylene group.

2. The functionalized nanodiamond of claim 1 , wherein the at least one naturally occurring basic amino acid is selected from one or more of lysine, arginine and histidine, and an analog or derivative thereof.

3. The functionalized nanodiamond of claim 1 , wherein the at least one naturally occurring basic amino acid and the linker group together form the structure:

Wherein Y is selected from —(CH 2 ) 4 NH 2 ,

and —(CH 2 ) 3 NHC(NH)NH 2 .

4. The functionalized nanodiamond of claim 1 , wherein the at least one naturally occurring basic amino acid and the linker group together form the structure:

wherein Y and Y′ are, independently, selected from —(CH 2 ) 4 NH 2 ,

and —(CH 2 ) 3 NHC(NH)NH 2 .

5. The functionalized nanodiamond of claim 1 , wherein the nanodiamond is prepared from a detonation nanodiamond.

6. The functionalized nanodiamond of claim 1 , wherein the nanodiamond has a diameter of about 1 nm to about 10 nm, about 3 nm to about 6 nm or about 4 nm to about 5 nm.

7. The functionalized nanodiamond of claim 1 , wherein the functionalized nanodiamond has a surface loading of about 0.1 mmol/g nanodiamond to about 10 mmol/g nanodiamond or about 1.7 mmol/g nanodiamond.

8. The functionalized nanodiamond of claim 1 , wherein the nanodiamond further comprises one or more additional amino acids covalently linked thereto, wherein the additional amino acids are selected from naturally occurring acidic amino acids and naturally occurring neutral amino acids, and analogs and derivatives thereof.

9. The functionalized nanodiamond of claim 8 , wherein the additional amino acids are selected from aspartic acid, glutamatic acid, lysyl methyl ester and histidyl methyl ester, and analogs and derivatives thereof.

10. The functionalized nanodiamond of claim 1 , wherein the nanodiamond further comprises one or more targeting moieties covalently linked thereto.

11. A composition comprising a functionalized nanodiamond of claim 1 and a carrier.

12. The composition of claim 11 , wherein the composition has a zeta potential of greater than about +30 mV.

13. The composition of claim 11 , wherein the composition has an average particle size of about 5 nm to about 50 nm or about 21 nm.

14. A complex comprising a functionalized nanodiamond of claim 1 reversibly bound to a nucleic acid.

15. The complex of claim 14 , wherein the nucleic acid has a therapeutic effect when administered to a subject.

16. The complex of claim 14 , wherein the ratio by weight of the functionalized nanodiamond to the nucleic acid is from about 20:1 to about 50:1 or about 40:1 to about 50:1.

17. A pharmaceutical composition comprising the complex of claim 15 and a carrier.

18. A method for delivering a nucleic acid to a cell, comprising administering a complex of claim 15 to the cell.

19. A method of eliciting an immune response in a subject in need thereof, comprising administering a complex of claim 15 to the subject.

Assignees

• Univ Saskatchewan

Inventors

• Badea Ildiko
• Verrall Ronald
• Chitanda Jackson M
• Kaur Randeep
• Alwani Saniya

Classifications

• A61K47/48884

  Human Necessities · mapped topic

• Y10T428/2982

  Particulate matter [e.g., sphere, flake, etc.] · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• C07C59/52

  a hydroxy or O-metal group being bound to a carbon atom of a six-membered aromatic ring · CPC title

• H01J49/0027

  Methods for using particle spectrometers · CPC title