ArticlePharmaceutics2022
Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a β-Blocker Potentiate Doxorubicin's Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer.
Article in Pharmaceutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Extracellular vesicles in breast cancer metastasis: functional insights and advances in single-EV analysis.Cancer metastasis reviews · 2026Review
- Preclinical Nanoparticle Approaches Targeting Tumor-Associated Macrophages in Breast Cancer: From Mechanisms to Therapeutic Strategies.International journal of nanomedicine · 2026Review
- Polarization-Specific Macrophage-Derived Extracellular Vesicles: Molecular Cargo, Tumor Microenvironment Remodeling, and Therapeutic Opportunities.International journal of nanomedicine · 2026Review
- Immunocyte reprogramming empowers live-cell drug delivery: Mechanistic insights, delivery strategies, and clinical perspectives.Acta pharmaceutica Sinica. B · 2026Review
- Macrophage-cancer cell crosstalk in breast cancer chemotherapy resistance.Medical oncology (Northwood, London, England) · 2025Review
- M1 Macrophage Extracellular Vesicles and TLR3 Agonist Nanoparticles Down-Regulate Immunosuppression and Metastasis via AKT/TAM in Triple-Negative Breast Cancer.Molecular carcinogenesis · 2025Article
- Extracellular vesicles: the "Trojan Horse" within breast cancer host microenvironments.Molecular cancer · 2025Review
- Article
- Anti-Inflammatory Macrophage-Derived Exosomes Modified With Self-Antigen Peptides for Treatment of Experimental Autoimmune Encephalomyelitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Interleukin-2 Surface Displayed M1 Macrophage-Derived Extracellular Vesicles for Modulating the Tumor Microenvironment.International journal of nanomedicine · 2025Article
- The dual effects of macrophage-derived extracellular vesicles on tumor cell behavior: mechanisms and clinical potential.Frontiers in oncology · 2025Review
- The impact of the tumor microenvironment on macrophages.Frontiers in immunology · 2025Review
- Role of Hyaluronic acid and its chemical derivatives in immunity during homeostasis, cancer and tissue regeneration.Seminars in immunopathology · 2024Review
- Extracellular Vesicles as Drug Delivery System for Cancer Therapy.Pharmaceutics · 2024Review
- Extracellular vesicles in cancer cachexia: deciphering pathogenic roles and exploring therapeutic horizons.Journal of translational medicine · 2024Review
- Extracellular vesicles: a rising star for therapeutics and drug delivery.Journal of nanobiotechnology · 2023Review
- Editorial for Special Issue: Advanced Technologies for Developing the State-of-the-Art Nanomedicines.Pharmaceutics · 2023Article
- Review
- Combination of CAR‑T cell therapy and radiotherapy: Opportunities and challenges in solid tumors (Review).Oncology letters · 2023Review
- Extracellular vesicles in the treatment and diagnosis of breast cancer: a status update.Frontiers in endocrinology · 2023Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
One of the main reasons for cancer's low clinical response to chemotherapeutics is the highly immunosuppressive tumor microenvironment (TME). Tumor-ass ociated M2 macrophages (M2-TAMs) orchestrate the immunosuppression, which favors tumor progression. Extracellular vesicles (EVs) have shown great potential for targeted therapies as, depending on their biological origin, they can present different therapeutic properties, such as enhanced accumulation in the target tissue or modulation of the immune system. In the current study, EVs were isolated from M1-macrophages (M1-EVs) pre-treated with hyaluronic acid (HA) and the β-blocker carvedilol (CV). The resulting modulated-M1 EVs (MM1-EVs) were further loaded with doxorubicin (MM1-DOX) to assess their effect in a mouse model of metastatic tumor growth. The cell death and cell migration profile were evaluated in vitro in 4T1 cells. The polarization of the RAW 264.7 murine macrophage cell line was also analyzed to evaluate the effects on the TME. Tumors were investigated by qRT-PCR and immunohistochemistry. MM1-DOX reduced the primary tumor size and metastases. NF-κB was the major gene downregulated by MM1-DOX. Furthermore, MM1-DOX reduced the expression of M2-TAM (CD-163) in tumors, which resulted in increased apoptosis (FADD) as well as decreased expression of MMP-2 and TGF-β. These results suggest a direct effect in tumors and an upregulation in the TME immunomodulation, which corroborate with our in vitro data that showed increased apoptosis, modulation of macrophage polarization, and reduced cell migration after treatment with M1-EVs combined with HA and CV. Our results indicate that the M1-EVs enhanced the antitumor effects of DOX, especially if combined with HA and CV in an animal model of metastatic cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.