Controlled release polymer nanoparticle containing bound nucleic acid ligand for targeting

1. A controlled release polymer nanoparticle, comprising;

a therapeutic or diagnostic agent incorporated in the controlled release polymer nanoparticle; and

a nucleic acid ligand comprising an oligonucleotide bound to the surface of the controlled release polymer nanoparticle that selectively binds to a target cell or tissue, and thereby delivers the controlled release polymer nanoparticle to the target cell or tissue;

wherein the controlled release polymer nanoparticle carries a neutral to negative charge on its surface; and

wherein the bound oligonucleotide has a folded three-dimensional conformation resulting from intramolecular interactions.

2. The controlled release polymer nanoparticle of claim 1 , wherein the nucleic acid ligand is prepared using L-enantiomeric nucleosides.

3. The controlled release polymer nanoparticle of claim 1 , wherein one or more internal nucleotides at the 3′-end, 5′-end, or both at the 3′- and 5′-end of the nucleic acid ligand are inverted to yield a 3′-3′ or a 5′-5′ nucleotide linkage.

4. The controlled release polymer nanoparticle of claim 1 , wherein one or more of the nucleotides of the nucleic acid ligand are bound to another nucleotide by a hydrocarbon linker or a polyether linker.

5. The controlled release polymer nanoparticle of claim 1 , wherein the nucleic acid ligand binds to a protein, a carbohydrate, a lipid or a nucleic acid.

6. The controlled release polymer nanoparticle of claim 5 , wherein the nucleic acid ligand binds to a protein selected from the group consisting of tumor-markers, integrins, cell surface receptors, transmembrane proteins, ion channels, membrane transport protein, enzymes, antibodies, and chimeric proteins.

7. The controlled release polymer nanoparticle of claim 5 , wherein the nucleic acid ligand binds to a nucleic acid selected from the group consisting of DNA, RNA, modified DNA, modified RNA, and combinations thereof.

8. The controlled release polymer nanoparticle of claim 1 , further comprising an agent for localization.

9. The controlled release polymer nanoparticle of claim 8 , wherein the localizing agent is a magnetic particle.

10. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle releases a therapeutic agent.

11. The controlled release polymer nanoparticle of claim 10 , wherein the therapeutic agent is selected from the group consisting of small molecule drugs, protein drugs, radionuclides, nucleic acid based drugs, and combinations thereof.

12. The controlled release polymer nanoparticle of claim 11 , wherein the therapeutic agent is a small molecule drug selected from the group consisting of an antibiotic, an antiviral agent, an antiparasitic agent, an anti-cancer agent, a radionuclide, an anticoagulant, an analgesic agent, an anesthetic agent, an ion channel potentiator, and ion channel inhibitor, an anti-inflammatory agent, and combinations thereof.

13. The controlled release polymer nanoparticle of claim 11 , wherein the therapeutic agent is a nucleic acid based drug selected from the group consisting of DNA, RNA, modified DNA, modified RNA, antisense oligonucleotides, expression plasmid systems, intact genes, intact or partially complementary DNA promoter regions of gene expression, intact or partially complementary DNA repressor regions of gene expression, intact or partially complementary DNA enhancer regions of gene expression, nucleotides, modified nucleotides, nucleosides, modified nucleosides, nucleic acid ligands, and combinations thereof.

14. The controlled release polymer nanoparticle of claim 1 , wherein the diagnostic agent is an iron oxide particle.

15. The controlled release polymer nanoparticle of claim 1 , wherein the diagnostic agent is a gadolinium complex.

16. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release nanoparticle releases a prophylactic agent.

17. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(lactic acid).

18. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(lactic acid) with a terminal carboxylic acid group or a terminal maleimide group.

19. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises PEG-poly(lactic acid) co-polymer.

20. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(lactic-co-glycolic acid).

21. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(lactic-co-glycolic acid) with a terminal carboxylic acid group or a terminal maleimide group.

22. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises PEG-poly(lactic-co-glycolic acid) co-polymer.

23. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(glycolic acid).

24. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises PEG-poly(glycolic acid) co-polymer.

25. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(caprolactone).

26. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises a polyanhydride.

27. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle is attached to the nucleic acid ligand by a linker.

28. The controlled release polymer nanoparticle of claim 27 , wherein the linker comprises an alkylene chain, a hydrocarbon chain, or a polyether chain.

29. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises poly(lactic acid)-PEG- maleimide and poly(lactic acid)-PEG.

30. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle has a zeta potential ranging between −17 and −100 mV.

31. The controlled release polymer nanoparticle of claim 1 , wherein the nucleic acid ligand is a spiegelmer.

32. The controlled release polymer nanoparticle of claim 1 , wherein the controlled release polymer nanoparticle comprises a polymer that is biologically degradable, chemically degradable, or both biologically and chemically degradable.

33. The controlled release polymer nanoparticle of claim 32 , wherein the controlled release polymer nanoparticle comprises a polymer selected from the group consisting of poly(lactic acid), derivatives of poly(lactic acid), PEGylated poly(lactic acid), poly(lactic-co-glycolic acid), derivatives of poly(lactic-co-glycolic acid), PEGylated poly(lactic-co-glycolic acid), a polyanhydride, poly(ortho esters), derivaties of poly(ortho esters), PEGylated poly(ortho esters), poly(caprolactone), derivatives of poly(caprolactone), PEGylated poly(caprolactone), poly(acrylic acid), derivatives of poly(acrylic acid), poly(urethane), derivatives of poly(urethane), and combinations thereof.

34. A composition comprising the controlled release polymer nanoparticle of claim 1 and a lipid.

35. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a controlled release polymer nanoparticle of claim 1 .

36. A method of delivering an agent to a target cell, comprising contacting a target cell or tissue with the controlled release polymer nanoparticle of claim 1 .

37. A method of treating a patient with cancer, comprising administering to the patient a controlled release polymer nanoparticle system of claim 1 .