Linkers for anchoring targeting ligands
View Patent ↗An improved linker which lacks chiral centers between a hydrophobic anchor for coupling to lipid-based particles and a targeting agent has suitable hydrophobic/hydrophilic properties for use in vivo.
1. A compound of the formula
targeting agent-SO 2 -phenylene-O(CH 2 ) n CONH(CH 2 ) n NHCO(CH 2 ) n —CONH(CH 2 ) n O(CH 2 CH 2 O) x CH 2 CH 2 OCZ-anchor (1)
wherein each n is independently 1-4;
x is an integer of 20-60;
Z is ═NH or ═O;
the targeting agent is a moiety containing an amino group or a hydroxyl group for coupling to the remainder of the molecule; and
the anchor is a lipophilic compound for embedding the compound in a lipid based particulate.
2. The compound of claim 1 wherein the targeting agent targets an integrin.
3. The compound of claim 1 wherein the targeting agent is an antibody or immuno-reactive fragment thereof, or
wherein the targeting agent is a ligand for a receptor.
4. The compound of claim 1 wherein the anchor is the residue of a phosphatidyl lipid.
5. The compound of claim 4 wherein the anchor is a residue of phosphatidyl ethanolamine.
6. The compound of claim 1 wherein x is an integer of 40-50.
7. A lipid-based particulate formulation wherein said lipid-based particles comprise a multiplicity of molecules of the compound of claim 1 .
8. The formulation of claim 7 wherein the particles further comprise a therapeutic or diagnostic agent.
9. The particulate formation of claim 8 wherein the therapeutic agent is a drug, and/or
wherein the diagnostic agent is a chelated metal for MRI imaging, or
wherein the therapeutic or diagnostic agent is a radionuclide.
10. The particulate formation of claim 8 wherein the lipid-based particles are liposomes, micelles, or nanoparticles containing cores consisting of liquid fluorocarbon coated with lipid/surfactant.
11. The particulate formation of claim 10 wherein the lipid-based particles are nanoparticles containing cores consisting of liquid fluorocarbon coated with lipid/surfactant.
12. A method to target a desired destination in a subject which comprises administering to said subject the formulation of claim 8 .