ArticleDrug delivery2022
Delivery of human natural killer cell-derived exosomes for liver cancer therapy: an in vivo study in subcutaneous and orthotopic animal models.
Article in Drug delivery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Natural Killer Cell-Derived Extracellular Vesicles as a Promising Immunotherapeutic Strategy for Cancer: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Natural Killer Cell-Derived Extracellular Vesicle Preparations Demonstrate Potent Antitumor Activity Against Human Glioblastoma In Vitro and In Vivo.Journal of extracellular biology · 2026Article
- The electrical and chemical hypoxia-optimized (ECHO) bioreactor system enables scalable production of functionally preserved NK-exosomes validated in a syngeneic lung cancer model.Drug delivery and translational research · 2026Article
- Natural Killer Cell-Derived Extracellular Vesicles Exhibit Cytotoxicity Against Bulk Tumor Cells and Cancer Stem Cells in Triple-Negative Breast Cancer.Nanomaterials (Basel, Switzerland) · 2026Article
- Tumor microenvironment-driven natural killer cell diversity: mechanisms and therapeutic opportunities.Cancer biology & medicine · 2026Review
- AS1411-Bivalent-Cholesterol-Anchor Equipped with Zinc Phthalocya-Nine Enables NK Cells Derived Exosomes to Realize Effective Tumor-Tropism Photodynamic Therapy.Pharmaceutics · 2026Article
- Antibody-Targeted Artificial T Cell and Natural Killer Cell Derived Vesicles for Cancer Immunotherapy.Journal of extracellular vesicles · 2026Article
- T-Cell-Derived Exosomes From Multi Core Granules Exhibit Superior Caspase-3-Mediated Tumor-Suppressive Activity Compared to Those From Multivesicular Bodies.Journal of extracellular vesicles · 2026Article
- Extracellular vesicle-based therapeutic strategies for spinal tumors and associated nerve damage: advances, challenges, and future directions.Frontiers in cell and developmental biology · 2026Review
- Immune cell-derived exosomes in cancer: double-edged mechanisms of antitumor immunity and tumor progression.Frontiers in immunology · 2026Review
- The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026Review
- Review
- NK Cell-Derived Small Extracellular Vesicles Armed With CLDN4-Targeting Peptides Potentiate Radiotherapy in Gastric Cancer.Journal of extracellular vesicles · 2025Article
- Bioengineered Extracellular Vesicles in Emerging Cancer Vaccine Platforms.Small science · 2025Review
- Chimeric Antigen Receptor Cell Therapy: Current Status and Its Potential in Aging and Alzheimer's Disease.International journal of molecular sciences · 2025Review
- NK-derived exosomes in anti-tumor strategies.Medical oncology (Northwood, London, England) · 2025Review
- Anti-Her2 CAR-NK92 Cells and Their Exosomes: Generation, Characterization, and Selective Cytotoxicity Against Her2-Positive Tumor Cells.International journal of molecular sciences · 2025Article
- Exosome-Based Theranostic for Gastrointestinal Cancer: Advances in Biomarker Discovery and Therapeutic Engineering.Small methods · 2025Review
- Exosomes in inflammation and cancer: from bench to bedside applications.Molecular biomedicine · 2025Review
- Extracellular Vesicle-Based Drug Delivery Systems in Cancer Therapy.International journal of molecular sciences · 2025Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exosomes are nanosized extracellular vesicles secreted by various cell types, including those of the immune system, such as natural killer (NK) cells. They play a role in intercellular communication by transporting signal molecules between the cells. Recent studies have reported that NK cell-derived exosomes (NK-exo) contain cytotoxic proteins-induced cell death. However, the characteristics and potential functions of NK-exo, especially for the liver cancer are poorly understood. In this study, we investigated the anti-tumor effects of NK-exo in the primary liver cancer, hepatocellular carcinoma (HCC), using the orthotopic and subcutaneous tumor model. We found that NK-exo expressed both typical exosomal markers (e.g. CD63, CD81, and Alix) and cytotoxic proteins (e.g. perforin, granzyme B, FasL, and TRAIL). NK-exo were selectively taken up by HCC cells (e.g. Hep3B, HepG2, and Huh 7). Interestingly, Hep3B cells induced the highest cytotoxicity compared with HepG2 and Huh7 cells, and substantially enhanced the apoptosis by NK-exo. Furthermore, we demonstrated that NK-exo inhibited the phosphorylation of serine/threonine protein kinases (e.g. AKT and ERK1/2), and enhanced the activation of specific apoptosis markers (e.g. caspase-3, -7, -8, -9, and PARP) in Hep3B cells. NK-exo also exhibit the active targeting ability and potent therapeutic effects in both orthotopic and subcutaneous HCC mouse models. Overall, these results suggest that NK-exo indicate strong anti-tumor effects in HCC, which are mediated by novel regulatory mechanisms involved in serine/threonine kinase pathway-associated cell proliferation and caspase activation pathway-associated apoptosis.
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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.