Compositions and methods for targeting cells
The present invention provides compositions and methods for targeting cells for therapeutic and/or diagnostic purposes, e.g., delivery of therapeutic and/or diagnostic agents to a cell. Nanoparticles and polymers functionalized with capture molecules, reporter molecules, and/or therapeutic agents are provided for the treatment or prevention of disease, including neurological diseases associated with neuroinflammation, and cancer.
1. A functionalized polymer comprising a first monomer: 2-Methacryloyloxyethyl phosphorylcholine (MPC), and a second monomer: methacrylate/amide polyethylene glycol (PEG) comprising an amine or azide covalently linked with
a translocator protein (TSPO) ligand precursor having the structure:
2. The functionalized polymer of claim 1 , wherein the molar ratio of the first monomer to the second monomer is about 25:3 to about 25:6.
3. The functionalized polymer of claim 1 , further comprising a third monomer: hydroxyethyl methacrylate polycaprolactone (HEMA-PCL) comprising a functionalized carboxyl group.
4. The functionalized polymer of claim 1 , wherein the monomers are polymerized using Reversible addition-fragmentation chain-transfer (RAFT) polymerization.
5. The functionalized polymer of claim 1 , further comprising a hydroxyethyl methacrylate-rhodamine (HEMA-Rhodamine) monomer.
6. The functionalized polymer of claim 1 , further comprising a hydroxyethyl methacrylate-succinate (HEMA-succinate) monomer.
7. The functionalized polymer according to claim 1 , wherein the functionalized polymer consists of carboxyl end groups, the first monomer, the second monomer, and optionally a third monomer: hydroxyethyl methacrylate polycaprolactone (HEMA-PCL) having a carboxylic acid conjugated to a fluorescent labelled chain or radioligand for positron emission tomography (PET) imaging.
8. The functionalized polymer according to claim 1 , wherein the functionalized polymer further comprises a third monomer: hydroxyethyl methacrylate polycaprolactone (HEMA-PCL) having a carboxylic acid conjugated to a fluorescent labelled chain or radioligand for positron emission tomography (PET) imaging.
9. The functionalized polymer according to claim 1 , wherein the functionalized polymer is a block copolymer.
10. A nanoparticle obtained from the functionalized polymer of claim 1 optionally loaded with a therapeutic agent, detectable reporter, or combination thereof.
11. A method of targeting a cell comprising contacting the cell with the nanoparticle of claim 10 wherein the cell comprises a TSPO receptor and the TSPO ligand targets the TSPO receptor.
12. The nanoparticle according to claim 10 , wherein the nanoparticle is loaded with iron.
13. A method of detecting a cell, the method comprising contacting the cell with the nanoparticle of claim 10 wherein the nanoparticle comprises a detectable reporter.
14. A method of delivering a therapeutic agent to a cell, the method comprising contacting the cell with the nanoparticle of claim 10 wherein the nanoparticle comprises the therapeutic agent.
15. A method of delivering a nucleic acid molecule to a cell, the method comprising contacting the cell with the nanoparticle of claim 10 , wherein the nanoparticle comprises a nucleic acid molecule.
16. A method of treating neuroinflammation in a subject, the method comprising administering to the subject the nanoparticle of claim 10 wherein the functionalized polymer further comprises a third monomer: hydroxyethyl methacrylate-deferoxamine (HEMA-deferoxamine), wherein the deferoxamine is bound to Zirconium 89 .
17. A method of treating neuroinflammation in a subject, the method comprising administering to the subject the nanoparticle of claim 10 , wherein the nanoparticle comprises iron.
18. A method of treating cancer in a subject, the method comprising administering to the subject the nanoparticle of claim 10 , wherein the nanoparticle comprises a chemotherapeutic agent selected from etoposide, busulfan, and lomustine.