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Updated: Aug 9, 2025
Modeling Brain Metastasis by Internal Carotid Artery Injection of Cancer Cells
Published on: August 2, 2022
All-stage targeted therapy for the brain metastasis from triple-negative breast cancer
Zimiao Luo1,2, Sunyi Wu1,2, Jianfen Zhou1,2
1Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai 201203, China.
Abstract:
Brain metastasis is a common and serious complication of breast cancer, which is commonly associated with poor survival and prognosis. In particular, the treatment of brain metastasis from triple-negative breast cancer (BM-TNBC) has to face the distinct therapeutic challenges from tumor heterogeneity, circulating tumor cells (CTCs), blood-brain barrier (BBB) and blood-tumor barrier (BTB), which is in unmet clinical needs. Herein, combining with the advantages of synthetic and natural targeting moieties, we develop a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome drug delivery system to address the all-stage targeted drug delivery for the whole progression of BM-TNBC. Inherited from the activated platelet, the hybrid liposomes still retain the native affinity toward CTCs. Further, the peptide-mediated targeting to breast cancer cells and transport across BBB/BTB are demonstrated in vitro and in vivo. The resultant delivery platform significantly improves the drug accumulation both in orthotopic breast tumors and brain metastatic lesions, and eventually exhibits an outperformance in the inhibition of BM-TNBC compared with the free drug. Overall, this work provides a promising prospect for the comprehensive treatment of BM-TNBC, which could be generalized to other cell types or used in imaging platforms in the future.
Insights
Researchers developed a novel drug delivery system using platelet-hybrid liposomes to treat brain metastasis from triple-negative breast cancer (BM-TNBC). This system effectively targets cancer cells and crosses biological barriers, improving treatment outcomes.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Brain metastasis is a severe complication of breast cancer, particularly triple-negative breast cancer (TNBC), with limited treatment options.
- Challenges in treating brain metastasis include tumor heterogeneity, circulating tumor cells (CTCs), and the blood-brain barrier (BBB)/blood-tumor barrier (BTB).
Purpose of the Study:
- To develop an advanced drug delivery system for comprehensive treatment of brain metastasis from triple-negative breast cancer (BM-TNBC).
- To overcome therapeutic challenges associated with BM-TNBC, including targeting and drug penetration.
Main Methods:
- Development of a "Y-shaped" peptide pVAP-decorated platelet-hybrid liposome system.
- Evaluation of targeting capabilities towards CTCs, breast cancer cells, and transport across BBB/BTB in vitro and in vivo.
- Assessment of drug accumulation in orthotopic tumors and brain metastatic lesions.
Main Results:
- The hybrid liposomes demonstrated affinity for CTCs and effective targeting of breast cancer cells.
- Successful transport across the BBB/BTB was confirmed.
- Significantly enhanced drug accumulation in both primary tumors and brain metastases was observed.
- The delivery platform showed superior efficacy in inhibiting BM-TNBC compared to free drugs.
Conclusions:
- The developed platelet-hybrid liposome system offers a promising approach for treating BM-TNBC.
- This platform demonstrates potential for broader applications in cancer therapy and imaging.
