Nanotube trans-membrane channels mimicking biological porins

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.

1 . A delivery method, comprising incubating a lipid-coated nanotube with a lipid membrane and thereby inserting the lipid-coated nanotube into the lipid membrane to form a channel across the lipid membrane; and delivering a moiety across the lipid membrane through the channel formed by the nanotube. 
     
     
         2 . The method of  claim 1 , wherein the nanotube comprises a material selected from carbon, molybdenum disulfide and boron nitride. 
     
     
         3 . The method of  claim 1 , wherein the nanotube has a length greater than 5 nm to about 30 nm and an internal diameter from about 0.5 nm to about 10 nm. 
     
     
         4 . The method of  claim 1 , wherein the nanotube has a length greater than a thickness of the lipid membrane. 
     
     
         5 . The method of  claim 1 , wherein a length of the nanotube is greater than 5 nm to about 15 nm. 
     
     
         6 . The method of  claim 1 , wherein the moiety is an imaging agent. 
     
     
         7 . The method of  claim 1 , wherein the moiety is a drug. 
     
     
         8 . The method of  claim 1 , wherein the moiety is a single stranded DNA. 
     
     
         9 . The method of  claim 8 , further comprising applying a voltage to opposite ends of the nanotube forming the channel across the lipid membrane to deliver the single stranded DNA across the lipid membrane through the channel formed by the nanotube. 
     
     
         10 . The method of  claim 8 , wherein the nanotube comprises a single-stranded polynucleotide attached to at least one end of the nanotube. 
     
     
         11 . The method of  claim 1 , wherein the lipid coating of the lipid-coated nanotube comprises comprise at least one of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1,2-diphytanoyl-sn-glycero-3-phosphocholine (DPhPC). 
     
     
         12 . The method of  claim 1 , wherein the lipid coating of the lipid-coated nanotube comprises the one or more phospholipids comprise 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). 
     
     
         13 . The method of  claim 1 , wherein the lipid coating of the lipid-coated nanotube comprises 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). 
     
     
         14 . The method of  claim 1 , wherein the lipid coating of the lipid-coated nanotube comprises one or more lipids 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 method of  claim 12 , wherein the lipid coating of the lipid-coated nanotube further comprises 1,2-dioleoyl-sn-Glycero-3-Phosphoethanolamine (DOPE), and cholesterol (Choi). 
     
     
         16 . The method of  claim 15 , 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). 
     
     
         17 . The method of  claim 2 , wherein the nanotube has a length greater than 5 nm to about 30 nm and an internal diameter from about 0.5 nm to about 10 nm. 
     
     
         18 . The method of  claim 17 , wherein the nanotube has a length greater than a thickness of the lipid membrane. 
     
     
         19 . The method of  claim 1 , comprising incubating a plurality of lipid-coated nanotube with the lipid membrane and thereby inserting the lipid-coated nanotubes of said plurality into the lipid membrane to form channels across the lipid membrane; and delivering a moiety across the lipid membrane through the channels formed by the nanotubes of said plurality. 
     
     
         20 . The method of  claim 1 , wherein the lipid-coated nanotubes of said plurality comprise a material selected from carbon, molybdenum disulfide, or boron nitride and have an internal diameter of from about 0.5 nm to about 10 nm, and a length greater than 5 nm to about 30 nm, wherein the length of the nanotubes is greater than a thickness of the lipid membrane 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 membrane.