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Pharmaceutics
Volume 14
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10.3390/pharmaceutics14010146
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Article

Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers

by
Yingnan Si
1,†,
Kai Chen
1,†,
Hanh Giai Ngo
1,
Jia Shiung Guan
2,
Angela Totoro
1,
Zhuoxin Zhou
1,
Seulhee Kim
2,
Taehyun Kim
2,
Lufang Zhou
1,2 and
Xiaoguang Liu
1,*
1
Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
2
Department of Medicine, University of Alabama at Birmingham (UAB), 703 19th Street South, Birmingham, AL 35294, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Pharmaceutics 2022, 14(1), 146; https://doi.org/10.3390/pharmaceutics14010146
Submission received: 14 December 2021 / Revised: 29 December 2021 / Accepted: 7 January 2022 / Published: 7 January 2022
(This article belongs to the Section Biopharmaceutics)
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Abstract

Triple-negative breast cancers (TNBCs) are heterogeneous and metastatic, and targeted therapy is highly needed for TNBC treatment. Recent studies showed that extracellular vesicles (EV) have great potential to deliver therapies to treat cancers. This study aimed to develop and evaluate a natural compound, verrucarin A (Ver-A), delivered by targeted EV, to treat TNBC. First, the surface expression of epidermal growth factor receptor (EGFR) and CD47 were confirmed with immunohistochemistry (IHC) staining of patient tissue microarray, flow cytometry and Western blotting. EVs were isolated from HEK 293F culture and surface tagged with anti-EGFR/CD47 mAbs to construct mAb-EV. The flow cytometry, confocal imaging and live-animal In Vivo Imaging System (IVIS) demonstrated that mAb-EV could effectively target TNBC and deliver the drug. The drug Ver-A, with dosage-dependent high cytotoxicity to TNBC cells, was packed in mAb-EV. The anti-TNBC efficacy study showed that Ver-A blocked tumor growth in both 4T1 xenografted immunocompetent mouse models and TNBC patient-derived xenograft models with minimal side effects. This study demonstrated that the targeted mAb-EV-Ver-A had great potential to treat TNBCs.
Keywords: triple-negative breast cancers; EGFR/CD47 targeting; extracellular vesicle; verrucarin A triple-negative breast cancers; EGFR/CD47 targeting; extracellular vesicle; verrucarin A

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MDPI and ACS Style

Si, Y.; Chen, K.; Ngo, H.G.; Guan, J.S.; Totoro, A.; Zhou, Z.; Kim, S.; Kim, T.; Zhou, L.; Liu, X. Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers. Pharmaceutics 2022, 14, 146. https://doi.org/10.3390/pharmaceutics14010146

AMA Style

Si Y, Chen K, Ngo HG, Guan JS, Totoro A, Zhou Z, Kim S, Kim T, Zhou L, Liu X. Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers. Pharmaceutics. 2022; 14(1):146. https://doi.org/10.3390/pharmaceutics14010146

Chicago/Turabian Style

Si, Yingnan, Kai Chen, Hanh Giai Ngo, Jia Shiung Guan, Angela Totoro, Zhuoxin Zhou, Seulhee Kim, Taehyun Kim, Lufang Zhou, and Xiaoguang Liu. 2022. "Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers" Pharmaceutics 14, no. 1: 146. https://doi.org/10.3390/pharmaceutics14010146

APA Style

Si, Y., Chen, K., Ngo, H. G., Guan, J. S., Totoro, A., Zhou, Z., Kim, S., Kim, T., Zhou, L., & Liu, X. (2022). Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers. Pharmaceutics, 14(1), 146. https://doi.org/10.3390/pharmaceutics14010146

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