Drug delivery vehicles for atherosclerosis nanomedicine
AssigneesNorthwestern University, The University of North Carolina at Chapel Hill
InventorsSamuel I. Stupp, Melina R. Kibbe, Mark R. Karver, Erica B. Peters, Miranda So, Neel Anand Mansukhani, Mazen Albaghdadi, Nick D. Tsihlis
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Abstract
Provided herein are peptide amphiphiles (PAs). In some embodiments, provided herein are targeting PAs comprising a PA backbone and a targeting moiety. In some embodiments, provided herein are therapeutic PAs comprising a PA backbone and a therapeutic agent. In some embodiments, the peptide amphiphiles are co-assembled into nanofibers. In some embodiments, the nanofibers may be used for the treatment of atherosclerosis or related disease.
Claims6
A peptide amphiphile comprising a hydrophobic tail, a structural peptide segment, a charged peptide segment, and a therapeutic agent for the treatment of atherosclerosis in a subject, wherein:
- a) the hydrophobic tail comprises an 8-24 carbon alkyl chain (C8-24),
- b) the structural peptide segment comprises V2A2 (SEQ ID NO:
- 8),
- c) the charged peptide segment comprises EE, EEE, or EEEE (SEQ ID NO:
- 11),
- d) the therapeutic agent is attached to the charged peptide segment by a cleavable linker selected from a ROS-sensitive proline linker, a glutathione-sensitive disulfide linker, and an MMP2/9-sensitive linker, and
- e) the therapeutic agent comprises an annexin A1 protein derivative or an LXR agonist, wherein the annexin A1 protein derivative is Ac2-26 or wherein the LXR agonist is selected from hypocholamide, T0901317, GW3965, N,N-dimethyl-3beta-hydroxy-cholenamide (DMHCA), T0901317, 22(R)-hydroxycholesterol and 24(S)-hydroxycholesterol.
Dependencies are inferred from the claim text.