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Metallosalphen-Covalent Organic Framework-Based Semiconducting Artificial Enzymes with Radio-Activable Antitumor

Yu Min1,2, Qian Li3,4, Zhenyang Zhao3

  • 1Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

ACS Nano
|October 17, 2025
PubMed

Insights

We developed novel semiconducting covalent organic frameworks coordinated with Ruthenium (SCOF-Ru) to enhance cancer therapy. These artificial enzymes produce reactive oxygen species (ROS) under X-ray irradiation, effectively suppressing tumor recurrence and metastasis.

Area of Science:

  • Materials Science
  • Nanotechnology
  • Biomedical Engineering

Background:

  • Reactive oxygen species (ROS)-catalytic therapies show promise for preventing tumor metastasis and recurrence.
  • Limited systemic immune activation often compromises the efficiency of current ROS-catalytic therapies.

Purpose of the Study:

  • To design and synthesize novel semiconducting artificial enzymes for enhanced ROS-catalytic efficiency and antitumor immunity.
  • To investigate the potential of Ruthenium-coordinated bis-Schiff base salphen-covalent organic frameworks (SCOF-Ru) in suppressing tumor metastasis and recurrence.

Main Methods:

  • De novo design and synthesis of SCOF-Ru with specific catalytic centers (Ru2N4O2).
  • Experimental and theoretical characterization of SCOF-Ru's electronic properties, including π-conjugation, electron transfer, and electron-hole separation.
  • Evaluation of ROS production capability under low-dose X-ray irradiation.
  • Assessment of radiosensitization effects, DNA repair inhibition, apoptosis induction, and calcium signaling pathway modulation.
  • In vivo validation of therapeutic efficacy and recurrence inhibition in various tumor models, including radiotherapy-resistant xenografts.

Main Results:

  • SCOF-Ru exhibits large π-conjugation, efficient electron transfer, and strong electron-hole separation.
  • The unique Ru2N4O2 catalytic centers enable superior ROS production under X-ray irradiation.
  • SCOF-Ru demonstrates high radiosensitization effects, inhibits DNA repair, and triggers apoptosis.
  • Therapeutic superiority and recurrence inhibition were validated in preclinical tumor models.
  • Combined with immune checkpoint blockade, SCOF-Ru showed potential for inhibiting distant tumor growth.

Conclusions:

  • The developed semiconducting SCOF-Ru acts as a radio-activable artificial enzyme with potent ROS-catalytic efficiency and antitumor immunity.
  • SCOF-Ru offers a promising strategy for suppressing tumor metastasis and recurrence, particularly in radiotherapy-resistant cases.
  • This innovative design opens a new avenue for treating malignant tumors through enhanced ROS-catalysis and immunomodulation.
Keywords:
antitumor immune responsesbiocatalytic nanomedicinescancer metastasis preventionenzyme-mimetic materialsreactive oxygen species

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