In situ oxidation-regulated self-assembly of peptides into transformable scaffolds for cascade therapy

Reactive oxygen species (ROS) are one of important biomarkers for pathological lesions and inspire development of ROS-responsive biomaterials for disease treatment. Here we report oxidation-regulated self-assembly of peptides into transformable scaffolds by in situ ROS generation for cascade cancer therapy. While the peptide is designed by rational incorporation of methionine residues and underwent efficient oxidation-controlled self-assembly, co-assembling the peptide with its derivatives functionalized with photosensitizer or chemodrug results in the scaffolds with combinatorial therapeutic effect. Photo-induced in situ ROS generation by the photosensitizer simultaneously endows the photodynamic therapy and promotes the morphological transition due to the methionine oxidation. In vivo studies confirm the significance of in situ ROS generation for the methionine oxidation and the morphological transition of the scaffolds, which further enhance tumor accumulation and penetration of therapeutics and thereby eradicating tumor arising from a cascade therapy process. Our findings demonstrate a new and versatile strategy for ROS-associated disease treatment in the future.