Nanotube trans-membrane channels mimicking biological porins

Patent metadata

Field	Value
Publication number	US-11439708-B2
Application number	US-201515503983-A
Country	US
Kind code	B2
Filing date	Oct 5, 2015
Priority date	Oct 6, 2014
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

Abstract

Provided herein is a nanopore structure, which in one aspect is a “carbon nanotube porin”, that comprises a short nanotube with an associated lipid coating. Also disclosed are compositions and methods enabling the preparation of such nanotube/lipid complexes. Further disclosed is a method for therapeutics delivery that involves a drug delivery agent comprising a liposome with a NT loaded with a therapeutic agent, introducing the therapeutic agent into a cell or a tissue or an organism; and subsequent release of the therapeutic agents into a cell.

First claim

The invention claimed is:

1. A liposome vesicle comprising a lipid bilayer, wherein the lipid bilayer of the liposome vesicle comprises (a) one or more phospholipids and (b) lipid-coated nanotubes comprised of a material selected from carbon, molybdenum disulfide, or boron nitride and having an internal diameter of from about 0.5 nm to about 10 nm, and having a length greater than 5 nm to about 30 nm, wherein the length of the nanotubes is greater than a thickness of the lipid bilayer of the liposome vesicle and more than 50% of the nanotubes have an angle of 15 degrees or less with respect to a direction perpendicular to a plane of the lipid bilayer of the liposome vesicle and wherein the nanotubes form channels across the lipid bilayer of the liposome vesicle.

2. The liposome vesicle of claim 1 , wherein the length of the nanotubes is greater than 5 nm to about 15 nm.

3. The liposome vesicle of claim 1 , wherein the one or more phospholipids comprise at least one of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC).

4. The liposome vesicle of claim 1 , further comprising a cargo moiety.

5. The liposome vesicle of claim 4 , wherein the cargo moiety is selected from the group consisting of a small molecule drug, an imaging agent, or a polynucleotide.

6. The liposome vesicle of claim 4 , wherein the cargo moiety is inside a lumen of the liposome vesicle.

7. A method of synthesizing a liposome vesicle of claim 1 , comprising segmenting a nanotube into shorter segmented nanotubes in the presence of an effective amount of one or more phospholipids and self-assembling the segmented nanotubes and the one or more phospholipids to form a lipid bilayer of the liposome vesicle, wherein the lipid bilayer of the liposome vesicle comprises (a) the one or more phospholipids and the segmented nanotubes, wherein the segmented nanotubes comprise a material selected from carbon, molybdenum disulfide, or boron nitride and having an internal diameter of from about 0.5 nm to about 10 nm, and having a length greater than 5 nm to about 30 nm, wherein the length of the nanotubes is greater than a thickness of the lipid bilayer of the liposome vesicle and more than 50% of the nanotubes have an angle of 15 degrees or less with respect to a direction perpendicular to a plane of the lipid bilayer of the liposome vesicle.

8. The method of claim 7 , wherein the segmenting is performed by ultrasonication.

9. The method of claim 7 , wherein the one or more phospholipids comprise 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).

10. The method of claim 7 , wherein the length of the segmented nanotubes is greater than 5 nm to about 15 nm.

11. The method of claim 7 , wherein the one or more phospholipids comprise at least one of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC).

12. The liposome vesicle of claim 1 , wherein the one or more phospholipids are selected from the group consisting of hydrogenated soy phosphatidylcholine (HSPC), lecithin, phosphatidylethanolamine, lysolecithin, lysophosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, cephalin, cardiolipin, phosphatidic acid, cerebro sides, distearoylphosphatidylethanolamine (DSPE), dioleoylphosphatidylcholine (DOPC), dipalmitoylphosphatidylcholine (DPPC), palmitoyloleoylphosphatidylcholine (POPC), palmitoyloleoylphosphatidylethanolamine (POPE) and dioleoylphosphatidylethanolamine 4-(N-maleimido-methyl)cyclohexane-1-carboxylate (DOPE-mal).

13. The liposome vesicle of claim 12 , wherein the lipid bilayer of the liposome vesicle further comprises (c) one or more non-phosphorous containing lipids.

14. The liposome vesicle of claim 13 , wherein the one or more non-phosphorous containing lipids are selected from the group consisting of stearylamine, dodecylamine, hexadecylamine, isopropyl myristate, triethanolamine-lauryl sulfate, alkyl-aryl sulfate, acetyl palmitate, glycerol ricinoleate, hexadecyl stereate, amphoteric acrylic polymers, polyethyloxylated fatty acid amides, DDAB, DODAC, DMRIE, DMTAP, DOGS, DOTAP (DOTMA), DOSPA, DPTAP, DSTAP, and DC-Chol.

15. The liposome vesicle of claim 1 , wherein the one or more phospholipids comprise 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC).

16. The liposome vesicle of claim 15 , wherein the lipid bilayer of the liposome vesicle further comprises 1,2-dioleoyl-sn-Glycero-3-Phosphoethanolamine (DOPE), and cholesterol (Choi).

17. The liposome vesicle of claim 16 , wherein the lipid bilayer of the liposome vesicle further comprises 1,2-dioleoyl-sft-Glycero-3-Phospho-L-Serine (DOPS) and 1,2-dioleoyl-sn-Glycero-3-Phosphoinositol-4,5-Bisphosphate (PI(4,5)P2).

18. The liposome vesicle of claim 17 , wherein the lipid bilayer further comprises 1,2-dioleoyl-sn-Glycero-3-Phosphoethanolamine-N-(Lissamine Pvhodamine B sulfonyl) (Rh-DOPE.

19. The liposome vesicle of claim 1 , wherein the lipid bilayer of the liposome vesicle is a charged lipid bilayer.

20. The liposome vesicle of claim 1 , wherein the lipid bilayer of the liposome vesicle is a non-charged lipid bilayer.

21. The liposome vesicle of claim 1 , wherein the length of the nanotubes is from 6.5 nm to about 30 nm.

22. The liposome vesicle of claim 21 , wherein at least 60% of the nanotubes have the angle of 15 degrees or less with respect to the direction perpendicular to the plane of the lipid bilayer of the liposome vesicle.

23. The liposome vesicle of claim 21 , wherein the one or more phospholipids comprise at least one of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC).

24. The liposome vesicle of claim 1 , wherein the length of the nanotubes is from 6.5 nm to about 15 nm.

25. The liposome vesicle of claim 24 , wherein at least 60% of the nanotubes have the angle of 15 degrees or less with respect to the direction perpendicular to the plane of the lipid bilayer of the liposome vesicle.

26. The liposome vesicle of claim 24 , wherein the one or more phospholipids comprise at least one of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC).

27. The liposome vesicle of claim 1 , wherein at least 60% of the nanotubes have the angle of 15 degrees or less with respect to the direction perpendicular to the plane of the lipid bilayer of the liposome vesicle.

28. The liposome vesicles of claim 1 , wherein the channels formed by the nanotubes are stable channels that provide transport of chemical species across the lipid bilayer of the liposome vesicle.

Assignees

• L Livermore Nat Security Llc
• Univ California
• Univ Pais Vasco

Inventors

• Noy Aleksandr
• Geng Jia
• Zhang Jianfei
• Frolov Vadim

Classifications

• C01B32/176

  Cutting · CPC title

• C01B32/17

  Purification · CPC title

• C01B32/172

  Sorting · CPC title

• C01B2202/36

  Diameter · CPC title

• C01B2202/34

  Length · CPC title