2. Academic Validation
  3. Neutrophil membrane-coated circular RNA nanoparticles for targeted immunotherapy in HER2-positive breast cancer brain metastasis

Neutrophil membrane-coated circular RNA nanoparticles for targeted immunotherapy in HER2-positive breast cancer brain metastasis

  • Cell Commun Signal. 2025 Jul 10;23(1):333. doi: 10.1186/s12964-025-02321-w.
Yunpeng Liu # 1 2,  Wei He # 3,  Xiaoju Li # 4,  Xiyan Lu 5,  Chihua Wu 6,  Yuan Gao 3,  Dong Fan 7,  Chao Dong 8,  Huadong Zhao 9
Affiliations

Affiliations

  • 1 The Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, People's Republic of China.
  • 2 Innovation Research Institute, Xijing Hospital, Air Force Medical University, Xi'an, 710032, People's Republic of China.
  • 3 State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Biotechnology Center, School of Pharmacy, Air Force Medical University, Xi'an, 710032, People's Republic of China.
  • 4 Bioinformatics Center of AMMS, Beijing, 100850, P.R. China.
  • 5 Department of Outpatient, The Second Affiliated Hospital, Fourth Military Medical University, Xi'an, 710038, People's Republic of China.
  • 6 Department of Breast Surgery, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
  • 7 Department of General Surgery, The Second Affiliated Hospital of the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. fandong1101@126.com.
  • 8 The Clinical Medical Research Center of Breast and Thyroid Tumor in Xinjiang, Department of Breast and Thyroid Surgery, The Affiliated Tumor Hospital of Xinjiang Medical University, Xinjiang Uygur Autonomous Region, Ürümqi, 830000, People's Republic of China. Dcdoctor@outlook.com.
  • 9 Department of General Surgery, The Second Affiliated Hospital of the Fourth Military Medical University, Xi'an, 710038, People's Republic of China. zhaolujy@fmmu.edu.cn.
  • # Contributed equally.
PMID: 40640807 DOI: 10.1186/s12964-025-02321-w
Abstract

Breast Cancer is the most prevalent malignancy worldwide, with approximately 50% of HER2-positive advanced breast Cancer patients eventually developing brain metastases, significantly reducing survival. Current HER2-targeted therapies, such as trastuzumab, exhibit limited efficacy in patients with brain metastases due to poor blood-brain barrier penetration and drug resistance. This study aimed to develop a novel strategy for treating HER2-positive breast Cancer brain metastases to improve overall survival. We engineered nanoparticles encapsulating circular RNA encoding the chemokine CXCL9 and an anti-PD-1 scFv, designed to target HER2-positive brain metastases. Our results demonstrate that these nanoparticles significantly enhance anti-tumor activity both in vitro and in vivo without exhibiting significant systemic toxicity. This approach improves the local tumor immune microenvironment while inducing lower systemic toxicity. In conclusion, we have established a platform of membrane-encapsulated circular RNA nanoparticles capable of targeting brain tumor lesions, showing potential for application in various brain disorders, including metastatic brain tumors. This novel approach offers a promising strategy for addressing the urgent need for effective treatments for HER2-positive breast Cancer brain metastases.

Keywords

Blood-brain barrier; Brain metastases; Circular RNA; HER2-positive breast cancer; Immunotherapy; Targeted drug delivery; Tumor microenvironment.

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