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Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers
Yingnan Si1, Kai Chen1, Hanh Giai Ngo1
1Department of Biomedical Engineering, University of Alabama at Birmingham (UAB), 1825 University Blvd, Birmingham, AL 35294, USA.
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.
Insights
Targeted extracellular vesicles (EVs) carrying verrucarin A show promise for treating triple-negative breast cancer (TNBC). This novel drug delivery system effectively targets and inhibits TNBC tumor growth with minimal side effects.
Area of Science:
- Oncology
- Nanotechnology
- Pharmacology
Background:
- Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies.
- Extracellular vesicles (EVs) are emerging as effective drug delivery vehicles for cancer treatment.
Purpose of the Study:
- To develop and evaluate a targeted drug delivery system for TNBC using EVs loaded with verrucarin A (Ver-A).
- To assess the efficacy and safety of Ver-A delivered via engineered EVs in preclinical TNBC models.
Main Methods:
- Confirmed EGFR and CD47 expression on TNBC cells.
- Engineered EVs surface-tagged with anti-EGFR/CD47 monoclonal antibodies (mAbs-EVs).
- Loaded mAbs-EVs with Ver-A and evaluated targeting and therapeutic efficacy in TNBC xenograft models.
Main Results:
- mAbs-EVs demonstrated effective targeting of TNBC cells and drug delivery.
- Ver-A exhibited dose-dependent cytotoxicity against TNBC cells.
- Ver-A delivered by mAbs-EVs significantly inhibited tumor growth in vivo with minimal side effects.
Conclusions:
- Targeted delivery of verrucarin A using engineered EVs (mAb-EV-Ver-A) presents a promising therapeutic strategy for TNBC.
- This approach offers a potential new avenue for treating metastatic and heterogeneous TNBC.
- The study highlights the potential of nanotechnology in advancing TNBC treatment.
