Tubular nanostructure targeted to cell membrane

Abstract

Devices, compositions, and methods are described which provide a tubular nanostructure or a composite tubular nanostructure targeted to a lipid bilayer membrane. The tubular nanostructure includes a hydrophobic surface region flanked by two hydrophilic surface regions. The tubular nanostructure is configured to interact with a lipid bilayer membrane and form a pore in the lipid bilayer membrane. The tubular nanostructure may be targeted by including at least one ligand configured to bind to one or more cognates on the lipid bilayer membrane of a target cell.

What is claimed is: 
     
         1 .- 119 . (canceled) 
     
     
         120 . A tubular nanostructure comprising:
 a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cell;   at least one cell type specific ligand attached to the tubular nanostructure and configured to bind one or more cell type specific cognates on the membrane; and   a binding moiety associated with one or both ends of the tubular nanostructure, the binding moiety having a structure to reversibly bind an agent including at least one of a therapeutic agent, a toxin, a genetic material, or a chemical, and wherein controlled dissociation of the agent from the binding moiety results in passage of the agent through the pore formed by the tubular nanostructure in the lipid bilayer membrane of the cell.   
     
     
         121 . The tubular nanostructure of  claim 120 , wherein the tubular nanostructure includes one or more of a carbon nanotube, cyclic peptide nanotube, crown ether nanotube, polymer nanotube, polymer/carbon nanotube, DNA nanotube, peptide nanotube, or inorganic nanotube. 
     
     
         122 . The tubular nanostructure of  claim 120 , wherein the hydrophilic surface region includes one or more of amines, amides, charged or polar amino acids, alcohols, carboxylic groups, oxides, ester groups, ether groups, or ester-ether groups, ketones, aldehydes, or derivatives thereof. 
     
     
         123 . The tubular nanostructure of  claim 120 , wherein the at least one cell type specific ligand is configured to bind one or more cell surface receptors or cell surface markers in or on the lipid bilayer membrane of the cell. 
     
     
         124 . The tubular nanostructure of  claim 120 , wherein the at least one cell type specific ligand is configured to bind at least one of a protein, a carbohydrate, a glycoprotein, a glycolipid, a sphingolipid, a glycerolipid or a metabolite thereof. 
     
     
         125 . The tubular nanostructure of  claim 120 , wherein at least one of the two hydrophilic surface regions are located at the one or both ends of the tubular nanostructure. 
     
     
         126 . The tubular nanostructure of  claim 120 , wherein the at least one cell type specific ligand includes at least a portion of an antibody, antibody-coated liposome, polynucleotide, polypeptide, receptor, viral plasmid, polymer, protein, small chemical compound, carbohydrate, lipid, toxin, pore-forming toxin, or glycoprotein. 
     
     
         127 . The tubular nanostructure of  claim 120 , further comprising a constitutively activatable marker attached to the tubular nanostructure, wherein the constitutively activatable marker is an activatable fluorescent marker having a chemical structure that constitutively fluoresces in response to a lipid environment, is a molecular beacon having a chemical structure that constitutively fluoresces in response to interacting with a target in or on the membrane, or is a pH sensitive fluorescent dye. 
     
     
         128 . A tubular nanostructure comprising:
 a hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cell;   at least one cell type specific ligand attached to the tubular nanostructure and configured to bind one or more cell type specific cognates on the membrane;   a constitutively activatable marker attached to the tubular nanostructure, the constitutively activatable marker including a molecular beacon having a chemical structure that constitutively fluoresces in response to interacting with at least one of a target in or on the membrane or a target within the extracellular matrix; and   a binding moiety associated with one or both ends of the tubular nanostructure, the binding moiety having a structure to reversibly bind an agent including at least one of a therapeutic agent, a toxin, a genetic material, or a chemical, and wherein controlled dissociation of the agent from the binding moiety results in passage of the agent through the pore formed by the tubular nanostructure in the lipid bilayer membrane of the cell.   
     
     
         129 . The tubular nanostructure of  claim 128 , wherein the tubular nanostructure includes one or more of a carbon nanotube, cyclic peptide nanotube, crown ether nanotube, polymer nanotube, polymer/carbon nanotube, DNA nanotube, peptide nanotube, or inorganic nanotube. 
     
     
         130 . The tubular nanostructure of  claim 128 , wherein the hydrophilic surface region includes one or more of amines, amides, charged or polar amino acids, alcohols, carboxylic groups, oxides, ester groups, ether groups, or ester-ether groups, ketones, aldehydes, or derivatives thereof. 
     
     
         131 . The tubular nanostructure of  claim 128 , wherein the at least one cell type specific ligand is configured to bind one or more cell surface receptors or cell surface markers in or on the lipid bilayer membrane of the cell. 
     
     
         132 . The tubular nanostructure of  claim 128 , wherein the at least one cell type specific ligand is configured to bind at least one of a protein, a carbohydrate, a glycoprotein, a glycolipid, a sphingolipid, a glycerolipid or a metabolite thereof. 
     
     
         133 . The tubular nanostructure of  claim 128 , wherein at least one of the two hydrophilic surface regions are located at the one or both ends of the tubular nanostructure. 
     
     
         134 . The tubular nanostructure of  claim 128 , wherein the at least one cell type specific ligand includes at least a portion of an antibody, antibody-coated liposome, polynucleotide, polypeptide, receptor, viral plasmid, polymer, protein, small chemical compound, carbohydrate, lipid, toxin, pore-forming toxin, or glycoprotein. 
     
     
         135 . The tubular nanostructure of  claim 128 , further comprising one or more elements associated with the one or both ends of the tubular nanostructure, the one or more elements having a size and a structure configured to physically and reversibly block the pore formed by the tubular nanostructure in the lipid bilayer membrane of the cell. 
     
     
         136 . A composite tubular nanostructure comprising:
 two or more nanotubes wherein at least one nanotube includes a hydrophobic surface region, each hydrophobic surface region flanked by two hydrophilic surface regions configured to form a pore in a lipid bilayer membrane of a cell;   at least one cell type specific ligand attached to the at least one nanotube and configured to bind one or more cell type specific cognates on the lipid bilayer membrane of the cell; and   a binding moiety associated with one or both ends of the at least one nanotube, the binding moiety having a structure to reversibly bind an agent including at least one of a therapeutic agent, a toxin, a genetic material, or a chemical, wherein controlled dissociation of the agent from the binding moiety results in passage of the agent through the pore formed by the at least one nanotube.   
     
     
         137 . The composite tubular nanostructure of  claim 136 , further comprising one or more active transport polypeptide elements configured to reversibly block the pore to control transport of molecules through the tubular nanostructure. 
     
     
         138 . The composite tubular nanostructure of  claim 136 , wherein at least two of the nanotubes have different diameters or different lengths. 
     
     
         139 . The composite tubular nanostructure of  claim 136 , wherein the binding moiety is a bifunctional antibody having a first portion and a second portion, the first portion capable of binding at one or both ends of the tubular nanostructure and the second portion capable of reversibly binding to the agent