Methionine residues were incorporated to confer responsiveness to reactive oxygen species (ROS), which are often present at elevated levels in the tumor microenvironment.[20] Utilizing the FDA‐approved DNA topoisomerase II poison Mitoxantrone (MTX) to induce DNA damage and cytotoxicity,[21] and Metformin (MET) to further enhance CD8+ T cell activity,[22] this study showcases the formulation of encapsulation of MTX and MET within the PD‐L1 downregulating hydrogel, followed by peritumoral administration for carrier‐free oncotherapy (Scheme 1). This evidence concerns the gene CD274 and neoplasm.