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Chemoradiotherapy-Integrated Tumor Cell-Derived Microparticles Mediate Tumor Eradication in Malignant Pleural

Minqi Zhou1,2,3, Lingyi Kong1,2,3, Weidong Zhong1,2,3

  • 1Cancer Center, Tongji Medical College, Union Hospital, Huazhong University of Science and Technology, Wuhan, China.

Journal of Extracellular Vesicles
|April 7, 2026
PubMed

Insights

New chemoradiotherapy-integrated tumor cell-derived microparticles (CR-MPs) show potent anti-cancer effects against malignant pleural effusion. This innovative therapy reprograms the tumor microenvironment and demonstrates significant potential for clinical translation.

Area of Science:

  • Oncology
  • Immunology
  • Nanomedicine

Background:

  • Malignant pleural effusion (MPE) is a serious complication of advanced cancer with poor prognosis.
  • Effective MPE treatment requires strategies that kill tumors and reprogram the immunosuppressive tumor microenvironment.
  • Irradiated tumor cell-derived microparticles (RT-MPs) have shown potential due to their inherent cytotoxicity and immune-activating properties.

Purpose of the Study:

  • To develop and evaluate novel chemoradiotherapy-integrated tumor cell-derived microparticles (CR-MPs) for enhanced treatment of MPE.
  • To investigate the anti-tumor mechanisms and therapeutic efficacy of CR-MPs, particularly methotrexate-loaded CR-MPs (CR-MPs@MTX).
  • To assess the potential of CR-MPs as a precision concurrent chemoradiotherapy strategy for MPE.

Main Methods:

  • CR-MPs were engineered by loading RT-MPs with chemotherapeutic agents (methotrexate, monomethyl auristatin E, doxorubicin).
  • In vitro studies assessed the tumoricidal activity of CR-MPs against various tumors.
  • In vivo studies utilized murine MPE models to evaluate tumor suppression, survival extension, biosafety, and combination therapy with immunotherapy.

Main Results:

  • CR-MPs demonstrated superior tumoricidal activity compared to RT-MPs and free drugs.
  • CR-MPs@MTX induced mitochondrial oxidative stress, immunogenic ferroptosis, M1 macrophage reprogramming, and dendritic cell stimulation via the cGAS-STING/NF-κB pathway.
  • In MPE models, CR-MPs suppressed tumor progression, extended survival, and showed good biosafety.
  • Combination therapy with immunotherapy achieved a 70% cure rate, induced durable immunological memory, and was effective against resistant tumors.

Conclusions:

  • CR-MPs represent a novel and effective therapeutic platform for MPE treatment.
  • This approach offers a promising precision concurrent chemoradiotherapy strategy with significant translational potential for MPE management.
  • CR-MPs overcome chemotherapy resistance and enhance anti-tumor immunity, paving the way for improved cancer care.
Keywords:
extracellular vesiclesferroptosisimmunotherapymalignant pleural effusionmicroparticlesradiotherapy

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