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Endogenous Amplification of Apoptosis via p53 Regulation using a Cascade Nanocatalytic Medicine

Tan Wu1, Xiaoyue Xu1, Dan Xu2

  • 1Department of Anesthesiology and Perioperative medicine, Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center For Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, School of Medicine, Shanghai Fourth People's Hospital, Tongji University, Shanghai, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|February 11, 2026
PubMed

Insights

This study introduces a novel nanocatalytic therapy using engineered metal-organic framework nanomedicine (MAL) to amplify cancer cell apoptosis. MAL effectively triggers DNA damage and cell cycle disruption, inhibiting tumor growth with good biocompatibility.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Therapy

Background:

  • Nanocatalytic therapy offers localized cancer treatment by converting substrates into cytotoxic agents.
  • Current limitations include a lack of durable, DNA-targeting cytotoxic mechanisms.
  • Enhanced apoptosis induction is crucial for effective cancer cell killing.

Purpose of the Study:

  • To develop a cascade nanocatalysis strategy for amplifying endogenous apoptosis in cancer cells.
  • To engineer a metal-organic framework nanomedicine (MOF-Au-L-Arginine, MAL) for this purpose.
  • To investigate MAL's mechanism of action and in vivo efficacy.

Main Methods:

  • Fabrication of MOF-Au-L-Arginine nanomedicine (MAL).
  • In vitro analysis of reactive oxygen species generation, DNA damage, cell cycle arrest, and apoptosis.
  • Genome-wide RNA sequencing to identify pathway activation (e.g., p53).
  • In vivo studies to evaluate tumor inhibition and biocompatibility.

Main Results:

  • MAL effectively catalyzes the generation of hydroxyl radicals and superoxide anions, leading to peroxynitrite formation.
  • Peroxynitrite induces significant DNA damage, impairs DNA repair, and disrupts the cell cycle.
  • MAL activates the p53 pathway and promotes mitochondrial-mediated apoptosis via the BAX/Bcl-2/caspase-3 axis.
  • In vivo studies demonstrated effective tumor growth inhibition with favorable biocompatibility.

Conclusions:

  • The developed cascade nanocatalysis strategy effectively amplifies endogenous apoptosis for cancer therapy.
  • MAL shows potential as a next-generation nanocatalytic therapeutic agent with enhanced efficacy and reduced toxicity.
  • Further research into MAL's therapeutic applications is warranted.
Keywords:
DNAMOFcolorectal cancernanocatalysisp53 proteinperoxynitrite

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