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Iron (Fe)‐based nanoparticles (NPs) have attracted considerable attention in nanomedicine research due to their enhancement effects in magnetic resonance imaging (MRI) and cancer therapy. Although zero‐valent Fe (Fe(0)) can serve as an active catalyst to decompose H2O2 into reactive oxygen species (ROS), its activity is compromised in physiological conditions due to its susceptibility to oxidation. Here it is reported that a 9 nm FeAu alloy NP system can efficiently stabilize Fe(0) in neutral pH solution, but release Fe(0) in tumor‐bearing environment, catalyzing H2O2 decomposition to ROS. Although Fe3O4 NPs and Au NPs are well‐known for their biocompatible, FeAu NPs effectively eliminate cancer cells at an IC50 as low as 15 µg mL−1 Fe. Further proteomics analysis reveals that FeAu NPs can concomitantly induce both ferroptosis and pyroptosis. Additional near‐infrared (NIR) irradiation further increases cell death and promotes maturation of dendritic cells within tumor‐draining lymph nodes and infiltration of helper T cells and cytotoxic T lymphocytes within tumor sites, resulting in significant reduction in tumor growth and metastasis. The studies demonstrate a great potential of FeAu NPs as a stable Fe(0) reservoir for pH/NIR controlled Fe(0) release and further for ferroptosis and pyroptosis co‐mediated tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Human umbilical cord mesenchymal stem cells (HUCMSCs) are applied for disease therapy as a new type of drug in many countries. Their effects are not only presented by live cells, but also apoptotic bodies or cell fragments of dead cells. Therefore, it is meaningful to determine the multiple fates of HUCMSCs in vivo. Although various probes combining different imaging modalities have been developed to label and trace transplanted HUCMSCs in vivo, the status of the cells (live, dead, or apoptotic) was not distinguished, and a thorough understanding of the multiple fates of HUCMSCs after transplantation in vivo is lacking. Therefore, a magnetic resonance (MR)/near infrared fluorescent (NIRF)/bioluminescence (BI) multi-modality imaging strategy was developed. Iron oxide nanoparticles (IONPs) were assembled into 100 nm nanoparticles using epigallocatechin gallate as a chemical linker to increase the MR signal and reduce the exocytosis of IONPs for direct cell labeling and longitudinal MR imaging tracking. Fluorescent probes for apoptosis (DEVD-Cy-OH) were also loaded in the above assemblies to monitor the cell status. Meanwhile, the cell surface was labeled with the fluorescent dye Cy7 via bioorthogonal reactions to visualize the NIRF signal. Luciferase was lentivirally transfected into live cells to generate bioluminescence. Such labeling did not affect either the viability, proliferation, migration, differentiation characteristics of HUCMSCs or their therapeutic effects on acute liver injury mice in vivo. The in vivo fates of HUCMSCs were monitored via MR/NIRF/BI multi-modality imaging in acute liver injury mice. Although MR and Cy7 signals aggregated in injured liver for 7 days, the BI signals persisted for less than 24 hours. There was an increase in DEVD-Cy-OH signals in the injured liver, but they were almost at the basal level. That means that HUCMSCs survive in mice for a short time, and the dead form of HUCMSCs accumulated in a large quantity and sustained for a long time, which might contribute to their therapeutic effect. [ABSTRACT FROM AUTHOR]

The enriched collagens in the extracellular matrix (ECM) of breast cancer substantially impede drug delivery. Halofuginone (HF), a potent antifibrotic agent, was effective to deplete the collagens and remodel the ECM by inhibiting the TGFβ pathway. However, the application of HF was hindered by its strong liver toxicity. Herein, mesoporous platinum (mPt) nanoparticles were constructed to load HF as theranostic nanoplatforms. mPt had a uniform spherical structure with a diameter of 79.83 ± 6.97 nm and an average pore diameter of 20 nm and exhibited good photothermal conversion efficiency of 62.4%. The obtained HF‐loaded nanoplatform (PEG@mPt‐HF) showed enhanced cytotoxicity through the combination of photothermal therapy and the anti‐TGFβ effect induced by HF. The animal imaging and histochemical assays confirmed the PEG@mPt‐HF could efficiently deliver HF to tumors (monitored by CT) and remodel the ECM by TGFβ pathway inhibition, which resulted in increased anti‐cancer efficacy. Importantly, the liver toxicity observed in HF‐treated mice was negligible in those treated by PEG@mPt‐HF. Overall, this study designed a theranostic nanoplatform to remodel the ECM with remarkably reduced systematic toxicity and enhance the therapeutic efficacy through combination treatment. [ABSTRACT FROM AUTHOR]