TCO conjugates and methods for delivery of therapeutic agents

1. A method for selectively delivering an effective amount of a therapeutic or diagnostic agent to a first location of a targeted organ or tissue in a patient, comprising the steps of:

(a) administering to the patient at the first location of the targeted organ or tissue a support composition comprising a biocompatible support and a first binding agent linked to the biocompatible support via a first linker, wherein the biocompatible support comprises at least one of a hydrogel, a polymer matrix, a metal, a ceramic, or a plastic, and the first binding agent comprises trans-cyclooctene or tetrazine;

(b) administering to the patient a bioactive composition comprising a therapeutic or diagnostic agent, a second binding agent comprising trans-cyclooctene or tetrazine complementary to the first binding agent, and a releasable linker linking the therapeutic or diagnostic agent and the second binding agent, such that the first and second binding agent bind to one another upon contact; and

(c) releasing the therapeutic or diagnostic agent, thereby delivering the therapeutic or diagnostic agent to the first location of the targeted organ or tissue.

2. The method of claim 1 , wherein the first binding agent is trans-cyclooctene and the second binding agent is tetrazine.

3. The method of claim 1 , wherein the second binding agent is 1,2,4,5-tetrazine.

4. The method of claim 1 , wherein the support composition is:

5. The method of claim 1 , wherein the support composition is:

and

the bioactive composition is selected from the group consisting of:

wherein R is selected from the group consisting of the therapeutic agent and the diagnostic agent.

6. The method of claim 1 , wherein the targeted organ or tissue is bone.

7. The method of claim 1 , wherein the concentration of the therapeutic or diagnostic agent at the first location of the targeted organ or tissue is greater than the concentration elsewhere in the patient.

8. The method of claim 1 , wherein the therapeutic agent is vancomycin.

9. The method of claim 1 , wherein the first binding agent and the first linker or second binding agent and the releasable linker together have the structure of:

10. The method of claim 9 , wherein the biocompatible support is selected from the group consisting of alginate, cellulose, chitosan, chitin, hyaluronic acid, chondroitin sulfate and heparin.

11. The method of claim 1 , wherein the first binding agent and the first linker or second binding agent and the releasable linker together have the structure of:

12. The method of claim 1 , wherein the first binding agent and the first linker or second binding agent and the releasable linker together have the structure of:

13. The method of claim 1 , wherein the support composition having the structure of:

wherein R is the biocompatible support.

14. The method of claim 1 , wherein the biocompatible support comprises a hydrogel.

15. The method of claim 1 , wherein the biocompatible support is selected from the group consisting of polysaccharide hydrogels, alginate, cellulose, hyaluronic acid, chitosan, chitin, hyaluronic acid, chondroitin sulfate, and heparin.

16. The method of claim 1 , wherein the biocompatible support is selected from the group consisting of alginate, chitin, hyaluronic acid, chitosan, and agarose.

17. The method of claim 1 , wherein the biocompatible support is selected from the group consisting of collagen, gelatin, elastin and elastin-like polypeptides, albumin, fibrin, poly(gamma-glutamic acid), poly(L-lysine), poly(L-glutamic acid), and poly(aspartic acid).

18. The method of claim 1 , wherein the support composition has the structure:

19. The method of claim 1 , wherein the biocompatible support comprises a polymer matrix.