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Author Spotlight: Advances in Evaluating Human Lung Epithelial Cells' Response to Metal-Organic Frameworks
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Mannose-doped metal-organic frameworks induce tumor cell pyroptosis via the PERK pathway

Nianqiang Jin1, Binhang Wang2, Xinyao Liu2,3,4

  • 1Department of Oral Pathology, School and Hospital of Stomatology, China Medical University, Shenyang, 110001, P. R. China.

Journal of Nanobiotechnology
|November 16, 2023
PubMed
Abstract

Insights

A novel mannose-modified nanosphere (M-FNM) effectively targets tumor cells, inducing pyroptosis and enhancing anti-tumor immunity. This approach shows promise for overcoming limitations of current cancer immunotherapies.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Research

Background:

  • Pyroptosis holds potential for enhancing anti-tumor immune responses.
  • Existing pyroptosis inducers face challenges like drug resistance, toxicity, and poor targeting.
  • Novel therapeutic strategies are needed to overcome these limitations in cancer treatment.

Purpose of the Study:

  • To develop a multifunctional nanosphere for precise tumor cell targeting.
  • To induce effective pyroptosis in cancer cells.
  • To overcome limitations associated with current pyroptosis-inducing agents.

Main Methods:

  • Synthesis of mannose-modified metal-organic framework (MOF) nanospheres: mannose-doped Fe3O4@NH2-MIL-100 (M-FNM).
  • Investigation of M-FNM cellular uptake via mannose receptor (MR)-mediated endocytosis in CAL27 cells.
  • Analysis of intracellular reactive oxygen species (ROS) generation, endoplasmic reticulum (ER) stress, and the PERK-eIF2α-ATF4-CHOP signaling pathway activation.
  • Evaluation of in vivo anti-tumor efficacy and immune microenvironment modulation.

Main Results:

  • M-FNM successfully entered CAL27 cells through MR-mediated endocytosis, increasing intracellular ROS.
  • This ROS surge triggered ER stress and activated the CHOP signaling pathway, leading to Caspase-1 activation and pyroptosis induction.
  • In vivo studies demonstrated M-FNM's effective tumor targeting, significant anti-tumor effects, and promotion of T lymphocyte infiltration, reshaping the tumor immune microenvironment.

Conclusions:

  • M-FNM significantly inhibited tumor growth.
  • This novel M-FNM-based pyroptosis induction strategy offers a promising new direction for developing effective cancer immunotherapies.
Keywords:
Anti-tumorER stressGSDMDImmunotherapyPyroptosis

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