Perylene‐Based Reactive Oxygen Species Supergenerator for Immunogenic Photochemotherapy against Hypoxic Tumors

Reactive oxygen species (ROS) can act as cytotoxic radicals to directly kill tumor cells and concurrently trigger immunogenic cell death (ICD) to efficiently achieve tumor therapy. Thus motivated, we herein present one perylene monoamide‐based ROS supergenerator (PMIC‐NC) that not only induces hypoxia‐enhanced Type‐I ROS burst aided by proton transients but also triggers Type‐I/II ROS production by electron or energy transfer under near‐infrared (NIR) light irradiation and also elicits a strong ICD effect. More interesting, the mitochondria‐ and lung‐specific distribution of PMIC‐NC also boosts the tumor therapeutic efficiency. As a result, PMIC‐NC was employed for NIR‐triggered photodynamic therapy, hypoxia‐enhanced chemotherapy and also displayed robust immunogenicity for systemic tumor eradication. This work thus contributes one proof‐of‐concept demonstration of perylene as an integrated therapeutic platform for efficient immunogenic photochemotherapy against hypoxic tumors. This work provides new insight and design guidelines for the construction of reactive oxygen species supergenerators by molecular engineering. An integrated perylene therapeutic platform was developed that efficiently realizes immunogenic photochemotherapy against hypoxic tumors.