Nanocarriers and their processing for diagnostics and therapeutics
The compositions and methods of the invention provide compositions and methods for preferential targeting of tissues to delivery therapeutic or diagnostic agents. For example, such compounds are useful in the treatment of joint disorders those affecting articulating joints, e.g., injury-induced osteoarthritis as well as autoimmune diseases affecting joint tissue such as rheumatoid arthritis.
1. A nanopiece for selective drug delivery to a bodily tissue comprising a compound of formula I or formula II or a combination thereof, and a nucleic acid:
wherein, X is CH or N;
R 2 is hydrogen or a linker group;
Y is absent when R 2 is hydrogen or is an amino acid side chain, amino acid or polypeptide; and
R 1 is hydrogen or aliphatic,
wherein the nanopiece has a size in at least one dimension between 0.1 nm and 150 nm,
wherein a ratio of the compound to nucleic acid ranges from 4.4 to 30 μg compound per to 0.1 nmol of the nucleic acid,
wherein the nanopiece is positively charged at pH 7-7.5.
2. The nanopiece of claim 1 , wherein the nucleic acid is a diagnostic agent or a therapeutic agent.
3. The nanopiece of claim 1 , wherein the nanopiece has a net positive charge of a Zeta potential >+8 mV.
4. The nanopiece of claim 1 , wherein the compound is selected from:
5. The nanopiece of claim 1 , wherein R 2 comprises an amino acid side chain or is selected from:
6. The nanopiece of claim 1 , wherein the compound is selected from
7. The nanopiece of claim 1 , wherein R 1 is C 1 to C 10 alkyl.
8. The nanopiece of claim 1 , wherein the nucleic acid comprises siRNA.
9. The nanopiece of claim 1 , wherein the nucleic acid comprises a molecular probe or a molecular beacon.
10. The nanopiece of claim 8 , wherein the nucleic acid comprises an IL-1 receptor siRNA.
11. The nanopiece of claim 9 , wherein the nucleic acid is the molecular beacon detecting MMP-13 or ADAMTS-5.
12. The nanopiece of claim 1 , further comprising one or more analgesic agents, anti-inflammatory agents, immunosuppresive agents, antifungal agents, antibiotic agents, lubricants, anti-cancer agents, NMDA receptor antagonists, or antiviral agents.
13. A method of making a nanopiece of claim 1 , comprising:
combining the compounds of Formula I or II and the nucleic acid, wherein the compounds form a nanotube and the nanotube and the nucleic acid form a complex; and
processing the complex comprising the nanotube and the nucleic acid to yield the positively charged nanopiece, said nanopiece comprising a size in at least one dimension of between 0.1 nm and 150 nm.
14. A composition comprising a nanopiece of claim 1 for selective delivery of a therapeutic drug or diagnostic agent to a target bodily tissue.
15. The nanopiece of claim 1 , wherein the nanopiece comprises a size of ≦30 nm in at least one dimension.
16. The nanopiece of claim 1 , wherein the nanopiece has a size of 1 to 30 nm in at least one dimension.
17. The nanopiece of claim 1 , wherein a ratio of the compound to nucleic acid ranges from 4.4 to 30 μg compound per to 0.1 nmol of the nucleic acid.
18. The nanopiece of claim 8 , wherein the nucleic acid comprises ADAMTS-5 siRNA.
19. The nanopiece of claim 8 , wherein the nucleic acid comprises Matrilin-3 siRNA.
20. The nanopiece of claim 8 , wherein the nucleic acid comprises a siRNA targeting a FGF receptor.
21. The nanopiece of claim 1 , wherein the nucleic acid comprises microRNA-365.
22. The nanopiece of claim 1 , wherein the nucleic acid comprises microRNA-1.46a.
23. The nanopiece of claim 1 , wherein the nucleic acid comprises microRNA-1.40.
24. The nanopiece of claim 1 , wherein the nucleic acid comprises an anti-microRNA.
25. The method of claim 13 , wherein the processing comprises altering pH, ionic strength or temperature, sonicating, heating and blending of the nanotube and the nucleic acid.
26. The method of claim 13 , wherein the processing is sonicating.