Compositions and methods for targeted delivery of therapeutic and/or diagnostic species
In one aspect, compositions are described herein. A composition described herein comprises a nanoparticle, a therapeutic species, and a linker joining the nanoparticle to the therapeutic species. The linker joining the nanoparticle to the therapeutic species comprises a Diels-Alder cyclo-addition reaction product. Additionally, in some embodiments, the nanoparticle is a magnetic nanoparticle.
1. A composition suitable for in vivo administration to a subject comprising:
a metal nanoparticle;
a therapeutic species; and
a linker joining the metal nanoparticle to the therapeutic species,
wherein the linker comprises a Diels-Alder cyclo-addition reaction product,
wherein the Diels-Alder cyclo-addition reaction product has a retro Diels-Alder reaction activation temperature between 30° C. and 180° C.,
wherein the metal nanoparticle has a plasmon resonance frequency in a visible region, in a near infrared region, or in an infrared region of the electromagnetic spectrum, such that upon administration of the composition to a biological compartment of the subject and applying to the biological compartment a wavelength of light matching the plasmon resonance frequency of the metal nanoparticle, the retro Diels-Alder reaction activation temperature is achieved resulting in a retro Diels-Alder reaction that cleaves the linker and releases the therapeutic species in the biological compartment of the subject.
2. The composition of claim 1 , wherein the metal nanoparticle is formed from iron, nickel, cobalt, manganese, platinum, silver or gold.
3. The composition of claim 1 , wherein the metal nanoparticle comprises at least two of silver, gold, and platinum.
4. The composition of claim 1 , wherein the therapeutic species comprises a small molecule, antibiotic, antifungal, nucleic acid, peptide, protein, or combinations thereof.
5. The composition of claim 4 , wherein the therapeutic species is a nucleic acid comprising a plasmid, small interfering RNA, micro-RNA, a miRNA mimic, or a combination thereof.
6. The composition of claim 1 , wherein the therapeutic species is an osteogenic modulator, a chondrogenic modulator, an endotheliogenic modulator, a myogenic modulator, or an anti-cancer agent.
7. The composition of claim 1 , wherein the linker is covalently bonded to the metal nanoparticle.
8. The composition of claim 1 , wherein the linker is covalently bonded to the therapeutic species.
9. The composition of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a furan.
10. The composition of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a thiophene.
11. The composition of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a pyrrole.
12. The composition of claim 1 , wherein the Diels-Alder cyclo-addition reaction product has a retro Diels-Alder reaction activation temperature between 40° C. and 85° C.
13. The composition of claim 1 , wherein the therapeutic species comprises miRNA-148b, a miRNA mimic of miRNA-148b, or a combination thereof.
14. The composition of claim 1 , wherein the therapeutic species comprises miRNA-34, a miRNA mimic of miRNA-34, or a combination thereof.
15. The composition of claim 1 , wherein the composition is suitable for use in treating or diagnosing a cancer, wherein the cancer is a prostate cancer, a skin cancer, or a lung cancer.
16. The composition of claim 1 , wherein the composition is suitable for use in treating or diagnosing a skin cancer.
17. The composition of claim 1 , wherein the composition is suitable for use in treating or diagnosing a lung cancer, wherein the lung cancer is a Ras-induced lung cancer.
18. The composition of claim 1 , wherein the therapeutic species comprises Paclitaxil, Afatinib, Dimaleate, Bortezomib, Carfilzomib, Doxorubicin, Fluorouracil, a miRNA mimic of miRNA-148b, a miRNA mimic of miRNA-135, a miRNA mimic of miRNA-124, a miRNA mimic of miRNA-101, a miRNA mimic of miRNA-29c, a miRNA mimic of miRNA-15a, a miRNA mimic of miRNA-34, or a combination thereof.
19. The composition of claim 1 , wherein the therapeutic species comprises simvastatin, strontium ranelate, miRNA 26a, miRNA 148b, miRNA 27a, miRNA 489, miR-9, miR-140, miR-30A, miR-210, miR-195, miR-155, miR-106b, miR-93, miR-25, miR-206, miR-1, siGDF-8, miR-133, miR-24 or miR-16.
20. The composition of claim 1 , wherein the therapeutic species are attached by two or more different linkers comprising different Diels-Alder cyclo-addition products.