Integrin targeted imaging agents
View Patent ↗Emulsions preferably of nanoparticles formed from high boiling liquid perfluorochemical substances, said particles coated with a lipid/surfactant coating are made specific to regions of activated endothelial cells by coupling said nanoparticles to a ligand specific for α v β 3 integrin, other than an antibody. The nanoparticles may further include biologically active agents, radionuclides, or other imaging agents.
1. A composition comprising an emulsion of nanoparticles, wherein said nanoparticles consist of liquid perfluorocarbon cores coated with lipid/surfactant, and
wherein said nanoparticles are coupled to a ligand specific for α v β 3 , which comprises the formula
and wherein the coupling of said nanoparticles to the ligand is through a covalent linkage, through a spacer, to a component of the lipid/surfactant coating, and
wherein said nanoparticles incorporate at least one biologically active agent.
2. The composition of claim 1 , wherein said residue is coupled through the spacer to a component of the lipid/surfactant coating that is a phosphatidyl lipid.
3. The composition of claim 2 , wherein the ligand coupled to the component of the lipid/surfactant coating is of the formula
4. The composition of claim 1 , wherein said biologically active agent is a hormone or pharmaceutical.
5. The composition of claim 4 , wherein the pharmaceutical compound is an antineoplastic agent, an analgesic, an anesthetic, a neuromuscular blocker, an antimicrobial agent, an antiparasitic agent, an antiviral agent, an interferon, an antidiabetic, an antihistamine, an antitussive, or an anticoagulant, or an antiproliferative.
6. The composition of claim 5 , wherein the pharmaceutical compound is an antiproliferative.
7. The composition of claim 6 , wherein the pharmaceutical compound is paclitaxel or rapamycin.
8. The composition of claim 1 , wherein said nanoparticles incorporate at least one magnetic resonance imaging (MRI) contrast agent.
9. The composition of claim 8 , wherein said MRI contrast agent is a chelated paramagnetic ion.
10. The composition of claim 9 , wherein the paramagnetic ion is gadolinium ion.
11. A kit for the preparation of an emulsion of nanoparticles targeted to tissue expressing α v β 3 which kit comprises at least one container that contains nanoparticles comprising a linking moiety for covalently coupling to a ligand specific for α v β 3 which comprises the formula
and at least one container that contains said ligand,
wherein said nanoparticles consist of liquid perfluorocarbon cores coated with lipid/surfactant.
12. A conjugate wherein a ligand of the formula
is covalently coupled to a lipid/surfactant through a spacer.
13. The compound of claim 12 , wherein the lipid/surfactant is a phospholipid.
14. The compound of claim 12 , wherein the linker comprises a polyalkylene glycol and/or a peptide.