A Near‐Infrared Light‐Responsive ROS Cascade Nanoplatform for Synergistic Therapy Potentiating Antitumor Immune Responses

Abstract Tumor occurrence is closely related to the unlimited proliferation and the evasion of the immune surveillance. However, it remains a challenge to kill tumor cells and simultaneously activate antitumor immunity upon spatially localized external stimuli. Herein, a robust tumor synergistic therapeutic nanoplatform is designed in combination with dual photosensitizers‐loaded upconversion nanoparticles (UCNPs) and ferric‐tannic acid (FeTA) nanocomplex. Dual photosensitizers‐loaded UCNPs can induce photodynamic therapy (PDT) effect by generation of cytotoxic reactive oxygen species (ROS) on demand under near‐infrared (NIR) light irradiation. FeTA can robustly respond to acidic tumor microenvironment to produce Fe 2+ and subsequently induce chemodynamic therapy (CDT) by reacting with H 2 O 2 in the tumor microenvironment. More importantly, the CDT/PDT synergy can not only exhibit significant antitumor ability but also induce ROS cascade to evoke immunogenic cell death. It increases tumor immunogenicity and promotes immune cell infiltration at tumor sites allowing further introduction of systemic immunotherapy responsiveness to inhibit the primary and distant tumor growth. This study provides a potential tumor microenvironment‐responsive nanoplatform for imaging‐guided diagnosis and combined CDT/PDT with improved immunotherapy responses and an external NIR‐light control of photoactivation.