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Layered Double Hydroxide-Based Sonosensitizer Triggers "Paraptosis+" Multidimensional Cell Death Network for

Yu Yang1, Tingting Hu2, Yanfang Zhu1

  • 1State Key Laboratory of Chemical Resource Engineering, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing, P. R. China.

Advanced Materials (Deerfield Beach, Fla.)
|January 29, 2026
PubMed

Insights

Researchers developed novel nanosheets to induce paraptosis (programmed cell death) and overcome tumor resistance. This sono-immunotherapy approach effectively eliminates cancer cells and inhibits tumor growth by combining multiple cell death pathways.

Area of Science:

  • Biomaterials Science
  • Cancer Therapy
  • Immunology

Background:

  • Paraptosis, a caspase-independent cell death, offers an alternative to overcome apoptosis resistance in cancer.
  • Current paraptosis inducers face limitations due to low reactive oxygen species (ROS) generation and insufficient anti-tumor efficacy.
  • Developing novel strategies to enhance paraptosis induction and anti-tumor activity is crucial for clinical translation.

Purpose of the Study:

  • To develop a novel inducer for paraptosis-mediated sono-immunotherapy to overcome limitations of existing treatments.
  • To investigate the synergistic effects of multi-modal cell death induced by the novel nanosheets.
  • To evaluate the efficacy of the developed sono-immunotherapy in inhibiting primary and distant tumor growth.

Main Methods:

  • Synthesis of defective nickel-doped ZnMo-layered double hydroxide nanosheets (DR-Ni-ZnMo-LDH).
  • Evaluation of DR-Ni-ZnMo-LDH as a sonosensitizer for ROS generation under ultrasound irradiation.
  • In vitro and in vivo studies to assess multi-modal cell death induction, immunogenic cell death, and tumor inhibition.

Main Results:

  • DR-Ni-ZnMo-LDH demonstrated superior singlet oxygen generation activity under ultrasound irradiation.
  • The ROS burst effectively induced paraptosis, apoptosis, and ferroptosis, synergistically eliminating apoptosis-resistant tumor cells.
  • Significant inhibition of primary (98.44%) and distant (88.53%) tumor growth was observed, alongside remodeling of the immunosuppressive tumor microenvironment.

Conclusions:

  • DR-Ni-ZnMo-LDH serves as an effective inducer for paraptosis-mediated sono-immunotherapy.
  • The multi-modal cell death strategy overcomes tumor resistance and immunosuppression.
  • This study presents a new material design paradigm for enhanced ROS-mediated sono-immunotherapy.
Keywords:
Paraptosisimmunogenic cell deathlayered double hydroxidessonosensitizertumor resistance

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