Compositions for delivery to and treatment of atherosclerotic plaques
Disclosed are compositions and methods for treatment of atherosclerosis and atherosclerotic plaques. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerosis. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerotic plaques. In particular, compositions comprising a plaque-homing element, a CendR-activating element, and a plaque-inhibiting element are disclosed.
1. A composition comprising a plaque-homing element, a CendR-activating element, and a plaque-inhibiting element, wherein the plaque-homing element is CX a RGX b RSX c C (SEQ ID NO:3), wherein X a and X b , are independently are any amino acid, and, independently, X c is any amino acid or is absent.
2. The composition of claim 1 , wherein the CendR-activating element is a peptide.
3. The composition of claim 1 , wherein the CendR-activating element is CGQKRTRGC (SEQ ID NO:2), GNKRTR (SEQ ID NO:7), CKRGAR (SEQ ID NO:9), CKRGSR (SEQ ID NO:10), CKRGNR (SEQ ID NO:11), CX a RGX b R (SEQ ID NO:13), KRGAR (SEQ ID NO:14), KRGSR (SEQ ID NO:15), KRGNR (SEQ ID NO:16), RGX b R (SEQ ID NO:12), X a RGX b R (SEQ ID NO:17), RPARPAR (SEQ ID NO:18), a peptide with the sequence X 1 X 2 X 3 X 4 at, or exposable at, the free C-terminal end of the peptide, wherein X 1 is R, K or H, wherein X 4 is R, K, H, or KG, and wherein X 2 and X 3 are each, independently, any amino acid), or an extended blood half-life LyP-1, wherein the extended blood half-life LyP-1 comprises the amino acid sequence GNKRTR (SEQ ID NO:7), wherein X a and X b independently are any amino acid.
4. The composition of claim 1 , wherein the plaque-inhibiting element is a peptide.
5. The composition of claim 1 , wherein the plaque-inhibiting element is CGQKRTRGC (SEQ ID NO:2 or an extended blood half-life LyP-1, wherein the extended blood half-life LyP-1 comprises the amino acid sequence GNKRTR (SEQ ID NO:7).
6. The composition of claim 1 , wherein one or more of the plaque-homing element, CendR-activating element, and plaque-inhibiting element is a peptide, wherein one or more of the one or more plaque-homing element, CendR-activating element, and plaque-inhibiting element that is a peptide conjugates to albumin in blood.
7. The composition of claim 1 , wherein one or more of the plaque-homing element, CendR-activating element, and plaque-inhibiting element is a peptide, wherein one or more of the one or more plaque-homing element, CendR-activating element, and plaque-inhibiting element that is a peptide is conjugated to a lipid.
8. The composition of claim 1 , wherein the composition is comprised in a micelle.
9. A method of treating atherosclerosis in a subject in need thereof, the method comprising administering a composition of claim 1 to the subject.
10. The method of claim 9 , wherein the subject is at risk of atherosclerosis.
11. The method of claim 9 , wherein the subject has atherosclerosis.
12. The composition of claim 1 , wherein X a is K, V, T, R, A, or Q.
13. The composition of claim 1 , wherein X a is K or T.
14. The composition of claim 1 , wherein X a is K.
15. The composition of claim 1 , wherein X b is A, S, G, N, T, or K.
16. The composition of claim 1 , wherein X b is A, S, or N.
17. The composition of claim 1 , wherein X b is A.
18. The composition of claim 1 , wherein X c is T, S, K, A, V, R, L, or absent.
19. The composition of claim 1 , wherein X c is T, S, or K.
20. The composition of claim 1 , wherein X c is T.
21. The composition of claim 1 , wherein X a is K, V, T, R, A, or Q, X b is A, S, G, N, T, or K, and X c is T, S, K, A, V, R, L, or absent.
22. The composition of claim 1 , wherein X a is K or T, X b is A, S, or N, and X c is T, S, or K.
23. The composition of claim 1 , wherein X a is K, X b is A, and X c is T.