Polymeric nanoparticles providing nucleic acids encoding TNF-α
The present invention relates to polymeric nanoparticles comprising a cytokine or a nucleic acid encoding for a cytokine, pharmaceutical compositions comprising the same, and methods for treating certain diseases comprising administering these polymeric nanoparticles to a subject in need thereof.
1. A composition comprising
a) polymeric nanoparticles comprising poly(lactic acid)-poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PLA-PEG-PPG-PEG) tetra-block copolymer; and
b) an isolated nucleic acid encoding a protein comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9.
2. The composition of claim 1 , wherein the PLA-PEG-PPG-PEG tetra-block copolymer is formed from chemical conjugation of PEG-PPG-PEG tri-block copolymer with PLA.
3. The composition of claim 1 , wherein the molecular weight of PLA is between about 10,000 and about 100,000 daltons.
4. The composition of claim 1 , further comprising a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, and polyarginine, wherein the peptide and the isolated nucleic acid form a complex.
5. The composition of claim 1 , further comprising a cationic cell-penetrating peptide.
6. The composition of claim 1 , further comprising an agent selected from the group consisting of doxorubicin, daunorubicin, decitabine, irinotecan, SN-38, cytarabine, docetaxel, triptolide, geldanamycin, 17-AAG, 5-FU, oxaliplatin, carboplatin, methotrexate, paclitaxel, indenoisoquinolines, and bortezomib.
7. The composition of claim 1 , wherein the polymeric nanoparticles further comprise a targeting moiety attached to the outside of the polymeric nanoparticles, and wherein the targeting moiety is an antibody, peptide, or aptamer.
8. The composition of claim 1 , wherein the polymeric nanoparticle comprises a tetra-block copolymer selected from the group consisting of PLA 12kDa -PEG-PPG-PEG-DNA, PLA 12kDa -PEG-PPG-PEG-Pt-DNA, PLA 72kDa -PEG-PPG-PEG-DNA and PLA 72kDa -PEG-PPG-PEG-Pt-DNA.
9. The composition of claim 1 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to nucleotides 404-874 of SEQ ID NO:11.
10. The composition of claim 1 , wherein the isolated nucleic acid comprises nucleotides 404-874 of SEQ ID NO:11.
11. The composition of claim 1 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to nucleotides 176-874 of SEQ ID NO:11.
12. The composition of claim 1 , wherein the isolated nucleic acid comprises nucleotides 176-874 of SEQ ID NO:11.
13. The composition of claim 1 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to the nucleotide sequence of SEQ ID NO:11.
14. The composition of claim 1 , wherein the isolated nucleic acid comprises the nucleotide sequence of SEQ ID NO:11.
15. The composition of claim 1 , wherein the isolated nucleic acid encodes the amino acid sequence of SEQ ID NO:9.
16. The composition of claim 1 , wherein the isolated nucleic acid encodes an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:10.
17. The composition of claim 1 , wherein the isolated nucleic acid encodes the amino acid sequence of SEQ ID NO:10.
18. A pharmaceutical composition comprising
a) polymeric nanoparticles comprising PLA-PEG-PPG-PEG tetra-block copolymer; and
b) an isolated nucleic acid encoding a protein comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 9.
19. The pharmaceutical composition of claim 18 , wherein the PLA-PEG-PPG-PEG tetra-block copolymer is formed from chemical conjugation of PEG-PPG-PEG tri-block copolymer with PLA.
20. The pharmaceutical composition of claim 18 , wherein the molecular weight of PLA is between about 10,000 and about 100,000 daltons.
21. The pharmaceutical composition of claim 18 , further comprising a peptide comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 1, 2, 3, 4, 5, 6, 7, 8, and polyarginine, wherein the peptide and the isolated nucleic acid form a complex.
22. The pharmaceutical composition of claim 18 , further comprising a cationic cell-penetrating peptide.
23. The pharmaceutical composition of claim 18 , further comprising an agent selected from the group consisting of doxorubicin, daunorubicin, decitabine, irinotecan, SN-38, cytarabine, docetaxel, triptolide, geldanamycin, 17-AAG, 5-FU, oxaliplatin, carboplatin, methotrexate, paclitaxel, indenoisoquinolines, and bortezomib.
24. The pharmaceutical composition of claim 18 , wherein the polymeric nanoparticles further comprise a targeting moiety attached to the outside of the polymeric nanoparticles, and wherein the targeting moiety is an antibody, peptide, or aptamer.
25. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to nucleotides 404-874 of SEQ ID NO:11.
26. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises nucleotides 404-874 of SEQ ID NO:11.
27. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to nucleotides 176-874 of SEQ ID NO:11.
28. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises nucleotides 176-874 of SEQ ID NO:11.
29. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises a nucleotide sequence at least 95% identical to the nucleotide sequence of SEQ ID NO:11.
30. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid comprises the nucleotide sequence of SEQ ID NO:11.
31. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid encodes the amino acid sequence of SEQ ID NO:9.
32. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid encodes an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:10.
33. The pharmaceutical composition of claim 18 , wherein the isolated nucleic acid encodes the amino acid sequence of SEQ ID NO:10.
34. The pharmaceutical composition of claim 18 , wherein the polymeric nanoparticle comprises a tetra-block copolymer selected from the group consisting of PLA 12kDa -PEG-PPG-PEG-DNA, PLA 12kDa -PEG-PPG-PEG-Pt-DNA, PLA 72kDa -PEG-PPG-PEG-DNA and PLA 72kDa -PEG-PPG-PEG-Pt-DNA.