A Peptide-Based Material for Therapeutic Carbon Monoxide Delivery

Abstract

We report on the preparation of the first material for therapeutic delivery of CO. A peptide amphiphile was synthesized with a covalently attached ruthenium tricarbonyl. Self-assembled nanofiber gels containing this peptide spontaneously released CO with prolonged release kinetics compared to soluble CO donors. Oxidatively stressed cardiomyocytes had improved viability when treated with this peptide, demonstrating its potential as a biodegradable gel for localized therapeutic CO delivery.

Fig. 1

(A) Absorbance spectra showing the conversion of dMb to COMb for CO-releasing PA 2. (B) Kinetics plot derived from these spectra for PA 2 and for CORM-3. The half-lives of release are the same within error, and the solid line is the fit to the PA 2 kinetics.

Fig. 2

Viability of cardiomyocytes after treatment with H₂O₂ and exposure to CO-releasing PA 2. Fluorescence images of PA 2, control PA 1, and H₂O₂ negative control are shown, with red indicating dead cells and green indicating live cells. Quantification of viability was performed by cell counting (n = 5–8 for each group). Significance for PA 2 and CORM-3 is shown relative to control and PA 1. All images are set to the same scale.

Fig. 3

SEM image of PA 2 mixed with diluent PA C₁₆V₂A₂E₂ and gelled by addition of CaCl₂. Scalebar = 0.5 μm.

Fig. 4

(A) Absorbance spectra showing the conversion of dMb to COMb for CO release from a gel containig PA 2. (B) Kinetics plot derived from these spectra, showing an 8-fold decrease in release rate compared with soluble PA 2.

Scheme 1

Synthesis of CO-releasing PA 2.