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bioinspired sulfur–fe–heme nanozyme nanomaterial-based bioorthogonal nanozymes thermo scientific k-alpha gambogic acid-iron nanozymes superior multi-enzyme activity amplifying feedback loop gambogic acid-iron nanozyme full size image transition-metal-based nanozymes c11-bodipy-based protocols annexin v-fitc/pi sds‒page x-ray photoelectron spectroscopy biodegradable mose2-polyvinylpyrrolidone nanoparticles excellent sustained-release capabilities detecting low-concentration nanozymes excellent tumor-killing efficacy ferroptosis-related markers gpx-4 gsh-px activity assay live/dead staining assay acquire high-resolution images gfd-mediated tumor killing privacy choices/manage cookies time-dependent release profiles context-dependent autophagy states authors scientific editing bmc autophagy-regulated signaling pathways multi-enzyme activities live/dead staining results ferroptosis-related marker expression iron-based nanozymes innovation team project multi-enzyme activity anhui province universities orthotopic tumor model ga-induced excessive autophagy concentration exceeded 60 µg/ml nat rev genet minimal nuclear envelopment methods mol biol orthotopic tumor inoculation excessive ros-induced ferroptosis multiple enzyme activities autophagy-dependent ferroptosis pathway representative tem image x-ray diffractometer probing lipid peroxidation tumor cell proliferation chem soc rev

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      headline:Gambogic acid-iron nanozymes as effective carriers for enhanced chemotherapy by inducing excessive autophagy and oxidative stress
      description:The complex dual role of autophagy provides new insights for enhancing tumor treatment efficacy. However, effectively regulating this process is key to enhancing therapeutic efficacy. To address this challenge, this study designed a gambogic acid-iron nanozyme (GAFe) as a novel carrier to enhance the effectiveness of chemotherapy drugs such as doxorubicin (DOX) by inducing excessive autophagy and oxidative stress. The synthesized nanoparticle (GAFe@DOX) is capable of slowly releasing its active components over a prolonged period within tumor tissues. Gambogic acid can induce excessive autophagy, while the multi-enzyme activity of GAFe and the activation of ferroptosis amplify and sustain excessive autophagy, thereby enhancing the chemotherapy effect of DOX. Meanwhile, ferroptosis activated via the GPX4 pathway by GAFe can synergize with excessive autophagy, amplifying oxidative stress and consequently enhancing the overall therapeutic efficacy. Characterization experiments confirmed the successful synthesis of GAFe@DOX and probe assays demonstrated its superior multi-enzyme activity. In vitro cell studies showed that GAFe@DOX effectively kills tumor cells, while in vivo animal experiments revealed its excellent biocompatibility and significant tumor growth inhibition. This study demonstrates a promising strategy to improve tumor therapeutic efficacy by modulating excessive autophagy and oxidative stress. This provides a novel and effective approach to improve the treatment of refractory tumors such as glioblastoma.
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         Autophagy
         Nanozymes
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         Ferroptosis
         Biotechnology
         Nanotechnology
         Molecular Medicine
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