All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Zimiao Luo; Sunyi Wu; Jianfen Zhou; Weixia Xu; Qianzhu Xu; Linwei Lu; Cao Xie; Yu Liu; Weiyue Lu

doi:10.1016/j.apsb.2022.03.026

All-stage targeted therapy for the brain metastasis from triple-negative breast cancer

Acta Pharm Sin B. 2023 Jan;13(1):359-371. doi: 10.1016/j.apsb.2022.03.026. Epub 2022 Apr 6.

Authors

Zimiao Luo^{1

2}, Sunyi Wu^{1

2}, Jianfen Zhou^{1

2}, Weixia Xu^{1

2}, Qianzhu Xu^{1

3

2}, Linwei Lu³, Cao Xie^{1

2}, Yu Liu^{1

2}, Weiyue Lu^{1

3

4

2}

Affiliations

¹ Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery, Fudan University, Shanghai 201203, China.
² State Key Laboratory of Medical Neurobiology, Collaborative Innovation Center for Brain Science, Fudan University, Shanghai 200032, China.
³ Department of Integrative Medicine, Huashan Hospital, Institutes of Integrative Medicine of Fudan University, Shanghai 200041, China.
⁴ Minhang Branch, Zhongshan Hospital and Institute of Fudan-Minghang Academic Health System, Minghang Hospital, Fudan University, Shanghai 201199, 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.

Keywords: Brain metastasis from breast cancer; Breast cancer; Cabazitaxel; Drug delivery system; Nanocrystal; Platelet-hybrid liposome; Targeted drug delivery; pVAP peptide.