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This study introduces FeDD nanozymes that use photothermal therapy and multienzyme cascade catalysis to treat cancer. These nanozymes self-supply hydrogen peroxide, enhancing reactive oxygen species generation for effective tumor cell apoptosis.

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Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Nanozyme-based catalytic therapy shows promise for cancer treatment by generating reactive oxygen species (ROS).
  • Tumor microenvironment's low hydrogen peroxide (H2O2) levels limit nanozyme efficacy.
  • Multifunctional nanozymes are needed to overcome these limitations and enhance therapeutic outcomes.

Purpose of the Study:

  • To develop multifunctional nanozyme nanoparticles (FeDD) for photothermally enhanced multienzyme cascade catalysis.
  • To investigate the synergistic effects of photothermal therapy (PTT), catalytic therapy, and chemotherapy for cancer treatment.
  • To address the H2O2 scarcity in the tumor microenvironment and enhance ROS generation.

Main Methods:

  • Self-assembly of FeDD nanoparticles from iron-coordinated polydopamine (PDA) and doxorubicin (DOX).
  • Evaluation of FeDD's superoxide dismutase (SOD)-, peroxidase (POD)-, and glutathione peroxidase (GPx)-like activities.
  • Assessment of PDA's intrinsic SOD-mimetic activity for H2O2 self-supply and DOX's role in enhancing ROS generation.
  • Investigation of the photothermal effect of PDA under near-infrared (NIR) irradiation.
  • In vitro and in vivo studies to evaluate antitumor efficacy and biocompatibility.

Main Results:

  • PDA demonstrated intrinsic SOD-mimetic activity, generating H2O2 and alleviating tumor hypoxia.
  • Iron coordination sites exhibited POD-like activity, converting H2O2 to cytotoxic hydroxyl radicals (•OH).
  • GPx-like activity depleted glutathione (GSH), amplifying oxidative stress.
  • DOX enhanced NADPH oxidase (NOx) activity, generating more superoxide anions (•O2−) to sustain the cascade.
  • FeDD nanozymes showed significant in vitro and in vivo antitumor efficacy, with complete tumor eradication in vivo upon NIR irradiation.

Conclusions:

  • FeDD nanozymes offer a promising platform for PTT-enhanced cascade catalytic tumor therapy.
  • The developed nanozyme effectively addresses H2O2 scarcity and enhances ROS production for synergistic cancer treatment.
  • FeDD exhibits high biocompatibility and potent antitumor efficacy, paving the way for novel cancer therapeutic strategies.