Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an important regulator for low density lipoprotein (LDL) particles. LDL buildup in cells is a major contributing factor for cardiovascular diseases. Thus, PCSK9 has been an attractive target for drug discovery efforts to prevent and limit the progression of pathological symptoms such as high blood pressure. We report a self-assembling peptide platform with the added PCSK9-mimic functionality for controlling the level of LDL particles in the issue and body fluids. The cholesterol-lowering aspect of our therapeutic strategy could be useful for localized treatment of tissues with high cholesterol mass, which may exert high pressure on the vasculature. The peptide hydrogel based on a beta-sheet secondary structure is injectable and possesses required viscoelastic properties. We characterize the multi-step self-assembly of the hydrogel through spectroscopic and microscopic investigation and elucidate the material properties through rheometry. Manipulation of the peptide sequence affords an interesting temperature responsive in the material property of the hydrogel which could be useful for the delivery of the therapeutic. The in vitro and in vivo experiments conducted provide important insight into the efficacy of the therapy and pave the way for a phase-I trial. The implantable material holds promise for prevention and treatment of many cardiovascular diseases, especially at early onset.

Biomimetic peptide hydrogels for modulating lipoprotein homeostasis

256th National Meeting (2018)

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