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Self-assembly, tunable hydrogel properties and selective anti- cancer activity of a carnosine-derived lipidated peptide

DOI: 10.1021/acsami.9b09065 DOI Help

Authors: Valeria Castelletto (University of Reading) , Charlotte J. C. Edwards-gayle (University of Reading) , Francesca Greco (University of Reading) , Ian W. Hamley (University of Reading) , Dr Jani Seitsonen (Aalto University) , Janne Ruokolainen (Aalto University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Acs Applied Materials & Interfaces

State: Published (Approved)
Published: August 2019
Diamond Proposal Number(s): 18523

Abstract: A novel lipopeptide C16KTTβAH was designed that incorporates the KTT tripeptide sequence from “Matrixyl” lipopeptides along with the bioactive βAH (β-alanine-histidine) carnosine dipeptide motif, attached to a C16 hexadecyl lipid chain. We show that this peptide amphiphile self-assembles above a critical aggregation concentration into β-sheet nanotape structures in water, PBS and cell culture media. Nanotape bundle structures were imaged in PBS, the bundling resulting from nanotape associations due to charge screening in the buffer. In addition, hydrogelation was observed and the gel modulus was measured in different aqueous media conditions, revealing tunable hydrogel modulus depending on concentration and nature of the aqueous phase. Stiff hydrogels were observed by direct dissolution in PBS and it was also possible to prepare hydrogels with unprecedented high modulus from low concentration solutions by injection of dilute aqueous solutions into PBS. These hydrogels have exceptional stiffness compared to previously reported β-sheet peptide-based materials. In addition, macroscopic soft threads can be drawn from concentrated aqueous solutions of the lipopeptides which contain aligned nematic structures. The anti-cancer activity of the lipopeptide was assessed using two model breast cancer cell lines, compared to two fibroblast cell line controls. These studies revealed selective concentration-dependent cytotoxicity against MCF-7 cancer cells in a mM concentration range. It was shown that this occurs below the onset of lipopeptide aggregation (i.e. below the critical aggregation concentration), indicating that the cytotoxicity is not related to self-assembly but is an intrinsic property of C16KTTβAH. Finally, hydrogels of this lipopeptide demonstrated slow uptake and release of the dye Congo red, a model diagnostic compound.

Journal Keywords: Lipopeptide; Peptide Amphiphile; Self-Assembly; Hydrogel; Anti-cancer

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: B21-High Throughput SAXS

Other Facilities: ESRF