TCO conjugates and methods for delivery of therapeutic agents
The present invention provides a method for selective delivery of a therapeutic or diagnostic agent to a targeted organ or tissue by implanting a biocompatible solid support in the patient being linked to a first binding agent, and administering a second binding agent to the patient linked to the therapeutic or diagnostic agent, such that the therapeutic or diagnostic agent accumulates at the targeted organ or tissue.
1. A method for selectively delivering an effective amount of a therapeutic or diagnostic agent to a targeted organ or tissue in a patient, comprising the steps of:
(a) administering to the patient at the targeted organ or tissue a support composition comprising a hydrogel, polymer, sugar-based biomaterial, or poly(amino-acid), each of which may be optionally modified, and a first binding agent linked to the polymer, sugar-based biomaterial, or poly(amino-acid) via a first linker, wherein 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 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 first binding agent is tetrazine and the second binding agent is trans-cyclooctene.
5. The method of claim 1 , wherein the first binding agent is 1,2,4,5-tetrazine.
6. The method of claim 1 , wherein the first binding agent together with the first linker or the second binding agent together with the second linker is
7. The method of claim 1 , wherein the organ or tissue is bone, cartilage, ligaments, tendons, intestines, muscles, nervous system, brain, spinal cord, heart, or nerves.
8. The method of claim 7 , wherein the targeted organ or tissue is bone.
9. The method of claim 1 , wherein the concentration of the therapeutic or diagnostic agent at the targeted organ or tissue is greater than the concentration elsewhere in the patient.
10. The method of claim 1 , wherein the patient is human.
11. The method of claim 1 , wherein the support composition comprises a polysaccharide hydrogel, alginate, cellulose, hyaluronic acid, chitosan, chitin, chondroitin sulfate, or heparin, each of which may be optionally modified.
12. The method of claim 1 , wherein the support composition is modified to comprise ethylene-oxy moieties, amines, esters, amides, ketone, urea, carbamate or carbonate functional groups.
13. The method of claim 1 , wherein the support composition comprises optionally modified alginate.
14. The method of claim 1 , wherein the support composition comprises optionally modified hyaluronic acid.