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 method of delivering a therapeutic species to a biological compartment, the method comprising:
disposing a composition in the biological compartment, the composition 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 170° C.; and
wherein the metal nanoparticle has a plasmon resonance frequency in a visible region or in an infrared region of the electromagnetic spectrum; and
initiating a retro Diels-Alder reaction to decompose the Diels-Alder cyclo-addition product, thereby severing the linker and decoupling the therapeutic species from the metal nanoparticle,
wherein initiating the retro Diels-Alder reaction comprises heating the metal nanoparticle to the retro Diels-Alder reaction activation temperature of the composition; and
wherein heating the metal nanoparticle to the activation temperature comprises exposing the metal nanoparticle to electromagnetic radiation comprising a frequency corresponding to the plasmon resonance frequency of the metal nanoparticle.
2. The method 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.
3. The method of claim 1 , wherein the metal nanoparticle is formed from silver or gold.
4. The method of claim 1 , wherein the metal nanoparticle comprises at least two of silver, gold, and platinum.
5. The method of claim 1 , wherein the Diels-Alder cyclo-addition reaction product has a retro Diels-Alder reaction activation temperature between 45° C. and 170° C.
6. The method of claim 1 , wherein the visible region comprises light having wavelengths from 300 nm to 700 nm.
7. The method of claim 1 , wherein the infrared region comprises light having wavelengths from 700 nm to 1 mm.
8. The method of claim 1 , wherein the visible region comprises light having wavelengths from 300 nm to 700 nm, and the infrared region comprises light having wavelengths from 700 nm to 1 mm.
9. The method of claim 1 , wherein the therapeutic species comprises a nucleic acid, peptide, protein, or combinations thereof.
10. The method of claim 1 , wherein the therapeutic species is a nucleic acid comprising a plasmid, small interfering RNA, micro-RNA, a miRNA mimic, or a combination thereof.
11. The method of claim 1 , wherein the linker is covalently bonded to the metal nanoparticle.
12. The method of claim 1 , wherein the linker is covalently bonded to the therapeutic species.
13. The method of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a furan.
14. The method of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a thiophene.
15. The method of claim 1 , wherein the Diels-Alder cyclo-addition reaction product is a reaction product of a dienophile and a pyrrole.
16. The method of claim 1 , wherein the Diels-Alder cyclo-addition reaction product has a retro Diels-Alder reaction activation temperature between 30° C. and 170° C.
17. The method of claim 1 , wherein the therapeutic species comprises miRN-148b, a miRNA mimic of miRN-148b, or a combination thereof.