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

Yingnan Si; Kai Chen; Hanh Giai Ngo; Jia Shiung Guan; Angela Totoro; Zhuoxin Zhou; Seulhee Kim; Taehyun Kim; Lufang Zhou; Xiaoguang Liu

doi:10.3390/pharmaceutics14010146

Pharmaceutics (Jan 2022)

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

Yingnan Si,
Kai Chen,
Hanh Giai Ngo,
Jia Shiung Guan,
Angela Totoro,
Zhuoxin Zhou,
Seulhee Kim,
Taehyun Kim,
Lufang Zhou,
Xiaoguang Liu

Affiliations

Yingnan Si: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Kai Chen: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Hanh Giai Ngo: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Jia Shiung Guan: Department of Medicine, University of Alabama at Birmingham (UAB), 703 19th Street South, Birmingham, AL 35294, USA
Angela Totoro: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Zhuoxin Zhou: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Seulhee Kim: Department of Medicine, University of Alabama at Birmingham (UAB), 703 19th Street South, Birmingham, AL 35294, USA
Taehyun Kim: Department of Medicine, University of Alabama at Birmingham (UAB), 703 19th Street South, Birmingham, AL 35294, USA
Lufang Zhou: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA
Xiaoguang Liu: Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA

DOI: https://doi.org/10.3390/pharmaceutics14010146
Journal volume & issue: Vol. 14, no. 1
p. 146

Abstract

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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.

Published in Pharmaceutics

ISSN: 1999-4923 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceutics/

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