Neutrophil membrane-coated circular RNA nanoparticles for targeted immunotherapy in HER2-positive breast cancer brain metastasis
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Published on: August 2, 2022
Yunpeng Liu1,2, Wei He3, Xiaoju Li4
1The Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xi'an, 710032, People's Republic of China.
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.
Insights
This study developed novel nanoparticles to treat HER2-positive breast cancer brain metastases. The engineered nanoparticles target tumors, enhance anti-tumor activity, and show reduced systemic toxicity, improving survival for patients with brain metastases.
Area of Science:
- Oncology
- Nanotechnology
- Immunotherapy
Background:
- Breast cancer is a leading malignancy globally, with HER2-positive subtypes frequently metastasizing to the brain.
- Brain metastases in HER2-positive breast cancer significantly reduce patient survival.
- Existing HER2-targeted therapies show limited efficacy against brain metastases due to poor blood-brain barrier penetration.
Purpose of the Study:
- To develop a novel therapeutic strategy for HER2-positive breast cancer brain metastases.
- To engineer nanoparticles capable of targeting and treating brain metastases.
- To improve overall survival in patients with HER2-positive breast cancer brain metastases.
Main Methods:
- Engineered nanoparticles encapsulating circular RNA encoding CXCL9 and an anti-PD-1 scFv.
- Designed nanoparticles to specifically target HER2-positive brain metastases.
- Evaluated nanoparticle efficacy and toxicity in vitro and in vivo.
Main Results:
- Nanoparticles demonstrated significant enhancement of anti-tumor activity.
- The approach showed reduced systemic toxicity.
- Improved local tumor immune microenvironment was observed.
Conclusions:
- Developed a novel platform of membrane-encapsulated circular RNA nanoparticles for targeting brain tumor lesions.
- This strategy shows potential for treating various brain disorders, including metastatic brain tumors.
- Offers a promising new approach for HER2-positive breast cancer brain metastases.
