Related Experiment Video
Updated: Jan 3, 2026
Scalable Biomanufacturing Workflow to Produce and Isolate Natural Killer Cell-Derived Extracellular Vesicle-Based Cancer Biotherapeutics
Published on: August 16, 2024
Macrophage-Derived Extracellular Vesicles as Drug Delivery Systems for Triple Negative Breast Cancer (TNBC) Therapy
Matthew J Haney1,2, Yuling Zhao1,2, Yeon S Jin2
1Center for Nanotechnology in Drug Delivery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Abstract:
Efficient targeted delivery of anticancer agents to TNBC cells remains one of the greatest challenges to developing therapies. The lack of tumor-specific markers, aggressive nature of the tumor, and unique propensity to recur and metastasize make TNBC tumors more difficult to treat than other subtypes. We propose to exploit natural ability of macrophages to target cancer cells by means of extracellular vesicles (EVs) as drug delivery vehicles for chemotherapeutic agents, paclitaxel (PTX) and doxorubicin (Dox). We demonstrated earlier that macrophage-derived EVs loaded with PTX (EV-PTX) and Dox (EV-Dox) target cancer cells and exhibited high anticancer efficacy in a mouse model of pulmonary metastases. Herein, we report a manufacture and characterization of novel EV-based drug formulations using different loading procedures that were optimized by varying pH, temperature, and sonication conditions. Selected EV-based formulations showed a high drug loading, efficient accumulation in TNBC cells in vitro, and pronounced anti-proliferation effect. Drug-loaded EVs target TNBC in vivo, including the orthotopic mouse T11 tumors in immune competent BALB/C mice, and human MDA-MB-231 tumors in athymic nu/nu mice, and abolished tumor growth. Overall, EV-based formulations can provide a novel solution to a currently unmet clinical need and reduce the morbidity and mortality of TNBC patients. Graphical Abstract Macrophage-derived extracellular vesicles (EVs) for targeted drug delivery to TNBC tumors. Chemotherapeutics with different water solubility (Dox or PTX, i.e. hydrophilic or hydrophobic drugs, respectively) were loaded into macrophage-derived EVs through parental cells (Dox), or into naïve EVs (Dox or PTX), and their antitumor efficacy was demonstrated in mouse orthotopic TNBC model.
Insights
Macrophage-derived extracellular vesicles (EVs) offer a novel drug delivery system for triple-negative breast cancer (TNBC). These engineered EVs efficiently target and reduce TNBC tumor growth, presenting a promising therapeutic strategy.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- Triple-negative breast cancer (TNBC) presents significant therapeutic challenges due to lack of specific markers and aggressive nature.
- Targeted drug delivery to TNBC cells is crucial for effective treatment and improved patient outcomes.
Purpose of the Study:
- To develop and characterize novel extracellular vesicle (EV)-based drug formulations for targeted delivery of chemotherapeutics to TNBC.
- To evaluate the efficacy of macrophage-derived EVs loaded with paclitaxel (PTX) and doxorubicin (Dox) in preclinical TNBC models.
Main Methods:
- Macrophage-derived EVs were engineered and loaded with PTX and Dox using optimized conditions (pH, temperature, sonication).
- Drug loading efficiency, in vitro cellular uptake in TNBC cells, and in vivo antitumor efficacy were assessed.
- Formulations were tested in orthotopic mouse models of TNBC (T11 and MDA-MB-231 tumors).
Main Results:
- Optimized EV formulations demonstrated high drug loading and efficient accumulation in TNBC cells.
- Drug-loaded EVs exhibited significant anti-proliferation effects in vitro.
- In vivo studies showed that drug-loaded EVs effectively targeted TNBC tumors and abolished tumor growth in both immune-competent and athymic mouse models.
Conclusions:
- Macrophage-derived EVs represent a viable and effective platform for targeted delivery of chemotherapeutics to TNBC.
- These EV-based formulations hold potential as a novel therapeutic strategy to address unmet clinical needs in TNBC treatment.
- This approach may reduce treatment-related morbidity and mortality in TNBC patients.
