CD8A and neoplasm: 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).