Compositions and methods for modifying the surface of cells and methods of use

Abstract

Described herein are compounds, compositions and methods for modification of the surface of a living cell with a therapeutically relevant targeting moiety. Also described herein are methods for treating disease states, such as acute myocardial ischemia or infarction, with said compositions, in a subject.

1 . A composition comprising the compound of formula (I)
   L-Y—X-T  (I)
   wherein   L is a phospholipid;   Y is a poly(ethylene glycol);   X is a linker derived from a reactive functional group; and   T is a targeting moiety adapted to bind to a target ligand.   
     
     
         2 . The composition of  claim 1 , wherein L is selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine. 
     
     
         3 . The composition of  claim 1 , wherein L is 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine. 
     
     
         4 . The composition of  claim 1 , wherein the poly(ethylene glycol) has a molecular weight between about 2 kDa and about 10 kDa. 
     
     
         5 . The composition of  claim 1 , wherein the poly(ethylene glycol) has a molecular weight of about 5 kDa. 
     
     
         6 . The composition of  claim 1 , wherein the reactive functional group is selected from the group consisting of maleimide, N-hydroxysuccinimide, hydroxyl, amino, carboxyl, thiol, silane, and azide. 
     
     
         7 . The composition of  claim 1 , wherein the target ligand is SDF-1. 
     
     
         8 . The composition of  claim 1 , wherein the target ligand is CRIP2. 
     
     
         9 . The composition of  claim 1 , wherein T is selected from the group consisting of a protein, a peptide, a glycoprotein, a glycopeptide, a steroid, a polysaccharide, a hormone, a cofactor, a nucleic acid, an antibody, a chimeric antigen receptor, and a drug. 
     
     
         10 . The composition of  claim 1 , wherein T is a protein. 
     
     
         11 . The composition of  claim 10 , wherein T is CXCR4. 
     
     
         12 . The composition of  claim 10 , wherein T is CRPPR. 
     
     
         13 . The composition of  claim 11 , wherein the reactive functional group is maleimide. 
     
     
         14 . The composition of  claim 1 , further comprising a cell bound to the compound of formula (I), wherein L interacts hydrophobically with the lipid bilayer wall of the cell. 
     
     
         15 . The composition of  claim 14 , wherein the cell is selected from the group consisting of a white blood cell, an endothelial cell, an hepatocyte, a kuppfer cell, an hepatic stellate cell, an allogeneic stem cell, a NK cell, a T cell, an endothelial progenitor cell, an hematopoietic stem cell, a pluripotent stem cell, an induced pluripotent stem cell, a lymphokine activated killer cell, a dendritic cell, and a mesenchymal stem cell. 
     
     
         16 . The composition of  claim 15 , wherein the cell is a mesenchymal stem cell. 
     
     
         17 . A method of treating myocardial infarction, comprising administering to a subject in need thereof the composition of  claim 16 , wherein T is CXCR4, and the target ligand is SDF-1. 
     
     
         18 . A method of localizing a cell to a location having associated therewith a target ligand, the method comprising delivering to the location a composition comprising the cell bound to the compound of formula (I):
   L-Y—X-T  (I)
   wherein   L is a phospholipid;   Y is a poly(ethylene glycol);   X is a linker derived from a reactive functional group; and   T is a targeting moiety adapted to bind to the target ligand.   
     
     
         19 . The method of  claim 18 , wherein L is selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine. 
     
     
         20 . The method of  claim 18 , wherein the poly(ethylene glycol) has a molecular weight between about 2 kDa and 10 kDa. 
     
     
         21 . The method of  claim 18 , wherein the poly(ethylene glycol) has a molecular weight of about 5 kDa. 
     
     
         22 . The method of  claim 18 , wherein the reactive functional group is selected from the group consisting of maleimide, N-hydroxysuccinimide, hydroxyl, amino, carboxyl, thiol, silane, and azide. 
     
     
         23 . The method of  claim 18 , wherein the target ligand is SDF-1. 
     
     
         24 . The method of  claim 18 , wherein the target ligand is CRIP2. 
     
     
         25 . The method of  claim 18 , wherein T is selected from the group consisting of a protein, a peptide, a glycoprotein, a glycopeptide, a steroid, a polysaccharide, a hormone, a cofactor, a nucleic acid, an antibody, a chimeric antigen receptor, and a drug. 
     
     
         26 . The method of  claim 25 , wherein T is CXCR4. 
     
     
         27 . The method of  claim 25 , wherein T is CRPPR. 
     
     
         28 . The method of  claim 26 , wherein the reactive functional group is maleimide. 
     
     
         29 . The method of  claim 18 , wherein the cell is selected from the group consisting of a white blood cell, an endothelial cell, a hepatocyte, a kuppfer cell, a hepatic stellate cell, an allogeneic stem cell, a NK cell, a T cell, an endothelial progenitor cell, an hematopoietic stem cell, a pluripotent stem cell, an induced pluripotent stem cell, a lymphokine activated killer cell, a dendritic cell, and a mesenchymal stem cell. 
     
     
         30 . The method of  claim 29 , wherein the cell is a mesenchymal stem cell.