Ultrasmall Ternary FePtMn Nanocrystals with Acidity‐Triggered Dual‐Ions Release and Hypoxia Relief for Multimodal Synergistic Chemodynamic/Photodynamic/Photothermal Cancer Therapy

Abstract Multimodal imaging‐guided synergistic anticancer strategies have attracted increasing attention for efficient diagnosis and therapy of cancer. Herein, a multifunctional nanotheranostic agent FePtMn‐Ce6/FA (FPMCF NPs) is constructed by covalently anchoring photosensitizer chlorin e6 (Ce6) and targeting molecule folic acid (FA) on ultrasmall homogeneous ternary FePtMn nanocrystals. Response to tumor microenvironment (TME), FPMCF NPs can release Fe 2+ to catalyze H 2 O 2 into •OH by Fenton reaction and simultaneously catalyze hydrogen peroxide (H 2 O 2 ) into O 2 to overcome the tumor hypoxia barrier. Released O 2 is further catalyzed into 1 O 2 under 660 nm laser irradiation with Ce6. Thus, the FPMCF NPs exhibit superior dual‐ROS oxidization capability including ferroptosis chemodynamic oxidization and 1 O 2 ‐based photodynamic oxidization. Interestingly, FPMCF NPs reveal strong photothermal conversion efficiency exposed to an 808 nm laser, which can assist dual‐ROS oxidization to suppress solid tumor remarkably. Additionally, Mn 2+ can be released from FPMCF NPs to enhance longitudinal relaxivity (T 1 ‐weighted magnetic resonance (MR) imaging) and Fe‐synergistic transverse relaxivity (T 2 ‐weighted MR imaging), which is convenient for diagnosis of solid tumors. Meanwhile, the fluorescent/photothermal (FL/PT) imaging function of FPMCF NPs can also accurately monitor tumor location. Therefore, FPMCF NPs with multimodal MR/FL/PT imaging‐guided synergistic chemodynamic/photodynamic/photothermal cancer therapy capability have potential bioapplication in bionanomedicine field.