Therapeutic platforms to induce reactive oxygen species (ROS) have been popularly applied in various tumor treatments, including the treatment of gliomas in the brain. However, there have been challenges in improving the precision, simplicity, and efficiency of these tumor theranostics. Herein, for the first time, we report a peptide-iron biomaterial based on a peptide-H2S donor conjugate AAN-PTC. This conjugate can be exclusively cleaved by legumain to release carbonyl sulfide (COS), which is hydrolyzed by carbonic anhydrase and subsequently releases H2S. Mass spectroscopy and electrochemical probe were applied to evaluate the degradation and H2S release. TEM and DLS were used to study the supramolecular morphology and properties. The delivery of H2S by AAN-PTC to both H9C2 cardiomyocytes and C6 glioma cell lines was confirmed quantitatively by in vitro fluorescence imaging studies. Furthermore, the peptide-iron complex was examined in a C6 glioma cell line, exhibiting an improved cell-killing effect by inducing toxic hydroxyl radical (OH) via a Fenton reaction. We hope this peptide-metal material will provide a novel gas-amplified, enzyme-responsive therapeutic platform for synergistic cancer treatment in the future.

Enhancing enzyme-triggered H2S-induced cytotoxicity in glioma via a supramolecular peptide-iron material

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