Reactive oxygen species (ROS)-based anticancer therapy methods were heavily dependent on specific tumor microenvironments such as acidity and excess hydrogen peroxide (H 2 O 2 ). In this work, an acidity-sensitive nanotheranostic agent (FePt@MnO)@DSPE-PEG5000-FA (FMDF NPs) was successfully constructed for MR imaging guided ferroptosis chemodynamic therapy (FCDT) of cancer. The FMDF NPs could specifically target folic acid (FA) receptor-positive tumor cells (HeLa etc.) and induce ferroptosis efficiently by rapidly releasing active Fe 2+ to catalyze intracellular H 2 O 2 into ROS based on Fenton reaction. On the other hand, the Mn 2+ could also be released due to acidity and further coordinate with GSH to enhance the longitudinal-transverse relaxivity (T 1 /T 2 -weighted MR imaging), which could obviously strengthen the contrast distinction between solid tumors and the surrounding tissue to accurately real-time monitor the tumor location. Furthermore, the in vivo anticancer study revealed that the growth of solid tumor models could be suppressed remarkably after treating with FMDF NPs and no obvious damage to other major organs. Therefore, the FMDF NPs were competent simultaneously as an enhanced imaging diagnosis contrast agent and efficient therapy agent for promoting more precise and effective treatment in the bionanomedicine field.

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.

In the tumor microenvironment (TME), an efficient Fenton reaction agent could have attractive tumor therapeutic efficacy, which is primarily based on delivering drugs to the tumor accurately and depressing undesirable side effects. Here, a metal− organic framework (MOF), with good biocompatibility and high loading capacity, with encapsulated FePt NPs (FePt-MOF NCs) and face-centered cubic (fcc)-FePt was successfully designed to eradicate cancer cells. The as-prepared multifunctional FePt-MOF NCs serve as a nanotheranostic agent for magnetic resonance/computed tomography (MR/CT) dual-modal imaging based on superparamagnetism and cancer therapy due to the well-known Fenton reactions. The drug nanodelivery system based on MOFs was able to safely deliver on the basis of intravenous administration. Because of its high sensitivity to acidic environments, the FePt-MOF would collapse and further release Fe and Pt ions, which would effectively trigger the Fenton reaction to produce plentiful toxic hydroxyl radicals in the acidic tumor microenvironment. On the one hand, the radicals could result in apoptotic cell death, whereas, on the other hand, they also lure the cumulation of lipid peroxides, causing tumor cell ferroptosis. These results indicated the great potential of the FePt-MOF NCs as a multifunction platform for tumor therapeutic and image applications.

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