Related Experiment Video

Updated: May 13, 2026

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?
14:20

Polymalic Acid-based Nano Biopolymers for Targeting of Multiple Tumor Markers: An Opportunity for Personalized Medicine?

Published on: June 13, 2014

Breaking the oncogene-immune suppression cycle through dual HER2 silencing and innate immune activation by

Yubei Duan1, Jiaxin Huang2, Tianping Huang3

  • 1Department of Pathology and Key Laboratory for Xinjiang Endemic and Ethnic Diseases (Ministry of Education), Shihezi University School of Medicine, The First Affiliated Hospital, Shihezi University, Shihezi, Xinjiang 832002, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.

Journal of Controlled Release : Official Journal of the Controlled Release Society
|May 11, 2026
PubMed

Insights

A novel nanoplatform, TanDNA@MnO2, combines HER2 gene silencing and immune activation to effectively treat HER2-positive breast cancer by inhibiting tumor growth and overcoming treatment resistance.

Area of Science:

  • Biomedical Engineering
  • Nanotechnology
  • Cancer Immunotherapy

Background:

  • HER2-positive breast cancer exhibits aggressive traits and resistance to current therapies due to immunosuppressive tumor microenvironments.
  • Existing HER2-targeted treatments face limitations including drug resistance and immune evasion, necessitating novel therapeutic strategies.

Purpose of the Study:

  • To develop and evaluate a multifunctional nanoplatform (TanDNA@MnO2) for combined gene silencing and immunotherapy in HER2-positive breast cancer.
  • To investigate the synergistic effects of HER2 gene silencing and cGAS-STING pathway activation mediated by the nanoplatform.

Main Methods:

  • Construction of TanDNA@MnO2 by biomineralizing manganese dioxide with tandem DNA (HER2-targeting DNAzyme and dsDNA motif).
  • Assessment of nanoplatform stability, tumor accumulation, and responsive release of Mn2+.
  • Evaluation of the nanoplatform's impact on HER2 expression, cGAS-STING pathway activation, immune cell modulation, and anti-tumor cytokine production.
  • In vivo studies to assess tumor growth inhibition and systemic toxicity.

Main Results:

  • TanDNA@MnO2 demonstrated favorable stability, tumor targeting, and pH/GSH-responsive Mn2+ release.
  • The nanoplatform effectively silenced HER2, inhibited proliferation, and activated the cGAS-STING pathway, enhanced by Mn2+.
  • TanDNA@MnO2 remodeled the tumor immune microenvironment, promoting M1 polarization, dendritic cell maturation, and CD8+ T cell infiltration.
  • Significant tumor growth inhibition with minimal systemic toxicity was observed in vivo.

Conclusions:

  • The TanDNA@MnO2 nanoplatform offers a dual-action approach combining gene silencing and immunotherapy for HER2-positive breast cancer.
  • This strategy effectively overcomes therapeutic resistance and immune evasion, showing promise for clinical translation.
  • The developed nucleic acid-metal oxide nanoplatform is a generalizable model for cancer therapy.
Keywords:
Combination therapyDrug resistanceOncogene silencingStimuli-responsive nanoparticlesTumor microenvironment

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