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Targeted Cancer Therapies

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Enhancing Triple-Negative Breast Cancer Radiotherapy via EZH2-Targeted Nanoplatform and Radionuclide Therapy.

Ruolin Wu^1,2,3, Yuyue Hou^1,2,3, Yongkang Gai^1,2,3

¹Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

Molecular Pharmaceutics

|November 22, 2025

Summary

This study developed a novel nanoplatform for triple-negative breast cancer (TNBC) treatment. Combining EZH2 inhibition with targeted radionuclide therapy enhanced antitumor immunity and efficacy in preclinical models.

Keywords:

EZH2 TNBC nanoplatform radionuclide tazemetostat

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Area of Science:

Oncology
Nanomedicine
Radiotherapy

Background:

Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
Targeted therapies and overcoming immunosuppression are critical challenges in TNBC treatment.

Purpose of the Study:

To develop a tumor microenvironment-responsive nanoplatform combining EZH2 inhibition and targeted radionuclide therapy (TRT) for enhanced TNBC treatment.
To evaluate the synergistic antitumor efficacy and immunomodulatory effects of this combined approach.

Main Methods:

Engineered a cancer cell membrane-camouflaged nanoplatform (CCm-HSA-Taz) encapsulating the EZH2 inhibitor Tazemetostat (Taz).
Co-administered the nanoplatform with [177Lu]Lu-based TRT in TNBC murine models.
Assessed nanoplatform stability, in vivo efficacy via imaging and histopathology, and immune response.

Main Results:

The CCm-HSA-Taz nanoplatform demonstrated favorable physicochemical properties and stability.
Combination therapy significantly enhanced immune response compared to monotherapies.
Observed increased apoptosis, improved antitumor immunity, reduced tumor glucose metabolism, and enhanced immune cell cytotoxicity.

Conclusions:

Developed a tumor microenvironment-adaptive nanoplatform for TNBC, delivering Taz to disrupt immunosuppression and improve radiotherapy sensitivity.
The combination strategy showed significant antitumor efficacy and enhanced immunity in preclinical models with no significant side effects.
FDA-approved components suggest potential for clinical translation.