Ph-sensitive peptides and their nanoparticles for drug delivery
A new nanoscale carrier made by one or more pH-sensitive peptides is provided for delivery of a biologically active substance. The peptides are composed of pH-sensitive hydrophilic and hydrophobic amino acids in the backbone. As the pH environment changes from physiological pH level to a weakly acidic environment such as near a tumor site (pH˜6.5-6.9), the peptides may dissolve, releasing the biological substance. Also provided are the delivery methods and related kits.
1. A peptide comprising one or more peptide subblocks, wherein each of the one or more peptide subblocks comprises an amino acid sequence and a linker, wherein the amino acid sequence is selected from the group consisting of HFFHGHFFHGHFFHGKK (SEQ ID NO: 9), Ac-HFFHGHFFHGHFFHGKK-NH2 (SEQ ID NO: 9), HFFHGHFFHGHFFHGHFFHGKK (SEQ ID NO: 10), HFFHGHFHFGHHFFGKK, and KGHFFHGHFFHGHFFH (SEQ ID NO: 8).
2. The peptide of claim 1 , wherein the peptide is soluble in an aqueous solution at a pH below 7.0.
3. The peptide of claim 1 , wherein the peptide is insoluble in an aqueous solution at a pH of 7.0-8.0.
4. The peptide of claim 1 , wherein the linker is an amino acid.
5. The peptide of claim 1 , wherein the linker is selected from the group consisting of alanine (A), cysteine (C), and glycine (G).
6. The peptide of claim 1 , wherein the linker is an alkyl chain having 3-8 carbons.
7. The peptide of claim 1 , wherein the peptide is conjugated to a hydrophilic block.
8. The peptide of claim 1 , wherein the peptide is conjugated to a functional block.
9. A nanoparticle comprising one or more peptides of claim 1 , wherein the nanoparticle is sensitive to a pH change.
10. The nanoparticle of claim 9 , wherein the nanoparticle is insoluble in an aqueous solution at a pH of 7.0-8.0.
11. The nanoparticle of claim 9 , wherein the nanoparticle is soluble in an aqueous solution at a pH below 7.0.
12. The nanoparticle of claim 9 , further comprising a biologically active substance.
13. The nanoparticle of claim 12 , wherein the biologically active substance is a drug selected from the group consisting of DNA, RNA, siRNA, miRNA, drugs, and imaging agents.
14. The nanoparticle of claim 12 , further comprising a hydrophilic surface moiety.
15. The nanoparticle of claim 14 , wherein the hydrophilic surface moiety is selected from the group consisting of hydrophilic ionic amino acids, nonionic amino acids, peptides, proteins, and polymers.
16. The nanoparticle of claim 9 , wherein the peptide is conjugated to a hydrophilic block.
17. The nanoparticle of claim 9 , wherein the peptide is conjugated to a functional block.
18. The nanoparticle of claim 9 , wherein the amino acid sequence is selected from the group consisting of HFFHGHFFHGHFFHGKK (SEC) ID NO: 9), Ac-HFFHGHFFHGHFFHGKK-NH2 (SEQ ID NO: 9), and KGHFFHGHFFHGHFFH (SEQ ID NO: 8).
19. A method for delivering the nanoparticle of claim 9 to a subject, comprising administering the nanoparticle to the subject.
20. The method of claim 19 , wherein the nanoparticle further comprises a biologically active substance, whereby the biological active substance is delivered to a target location in the subject.
21. A kit for delivering the nanoparticle of claim 9 to a subject, comprising the nanoparticle.
22. The kit of claim 21 , further comprising a biologically active substance.
23. The peptide of claim 1 , wherein the peptide is soluble in an aqueous solution at a pH below 6.8.
24. The peptide of claim 1 , wherein the peptide is insoluble in an aqueous solution at a pH of 6.8-8.0.
25. The nanoparticle of claim 9 , wherein the nanoparticle is insoluble in an aqueous solution at a pH of 6.8-8.0.
26. The nanoparticle of claim 9 , wherein the nanoparticle is soluble in an aqueous solution at a pH below 6.8.
27. The peptide of claim 1 , wherein the peptide is soluble in an aqueous solution at a pH below 7.2.
28. The peptide of claim 1 , wherein the peptide is insoluble in an aqueous solution at a pH of 7.2-8.0.
29. The nanoparticle of claim 9 , wherein the nanoparticle is insoluble in an aqueous solution at a pH of 7.2-8.0.
30. The nanoparticle of claim 9 , wherein the nanoparticle is soluble in an aqueous solution at a pH below 7.2.
31. The peptide of claim 1 , wherein the peptide is soluble in an aqueous solution at a pH below 6.6.
32. The peptide of claim 1 , wherein the peptide is insoluble in an aqueous solution at a pH of 6.6-8.0.
33. The nanoparticle of claim 9 , wherein the nanoparticle is insoluble in an aqueous solution at a pH of 6.6-8.0.
34. The nanoparticle of claim 9 , wherein the nanoparticle is soluble in an aqueous solution at a pH below 6.6.
35. The nanoparticle of claim 9 , further comprising a hydrophobic substance, wherein the solubility of the hydrophobic substance in an aqueous solution is enhanced.
36. The nanoparticle of claim 35 , wherein the hydrophobic substance is selected from the group consisting of lonidamine, paclitaxel, and bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES).
37. The peptide of claim 1 , wherein the amino acid sequence is selected from the group consisting of HFFHGHFFHGHFFHGKK (SEQ ID NO: 9), Ac-HFFHGHFFHGHFFHGKK-NH2 (SEQ ID NO: 9), and KGHFFHGHFFHGHFFH (SEQ ID NO: 8).