Compositions and methods for modifying the surface of cells and methods of use
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 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;
Y is a poly(ethylene glycol) having a molecular weight between about 2 kDa and about 10 kDa;
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 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine.
3. The composition of claim 1 , wherein the poly(ethylene glycol) has a molecular weight of about 5 kDa.
4. 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.
5. The composition of claim 1 , wherein the target ligand is SDF-1.
6. The composition of claim 1 , wherein the target ligand is CRIP2.
7. 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.
8. The composition of claim 1 , wherein T is a protein.
9. The composition of claim 8 , wherein T is CXCR4.
10. The composition of claim 8 , wherein T is CRPPR.
11. The composition of claim 9 , wherein the reactive functional group is maleimide.
12. 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.
13. The composition of claim 12 , 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.
14. The composition of claim 13 , wherein the cell is a mesenchymal stem cell.