☆ 4.7 Review

Extracellular vesicles derived from macrophages: Current applications and prospects in tumors

FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY (2022)

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Article Chemistry, Multidisciplinary

Hybrid-Membrane-Decorated Prussian Blue for Effective Cancer Immunotherapy via Tumor-Associated Macrophages Polarization and Hypoxia Relief

Lin Hou et al.

Summary: This study successfully addresses the limitations of tumor-associated macrophages and hypoxia conditions in cancer immunotherapy by developing a hollow mesoporous Prussian blue nanosystem with mannose decoration and hydroxychloroquine adsorption. In vivo experiments demonstrate that this system effectively inhibits tumor growth, induces macrophage polarization, promotes cytotoxic T lymphocytes infiltration, and alleviates hypoxia microenvironment.

ADVANCED MATERIALS (2022)

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Article Oncology

M2 macrophage-derived exosomes promote lung adenocarcinoma progression by delivering miR-942

Ke Wei et al.

Summary: The study demonstrates that exosomes derived from M2 macrophages play a role in promoting invasion and migration of LUAD cells through miRNA regulation, providing a new therapeutic target for metastatic LUAD.

CANCER LETTERS (2022)

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Article Biochemistry & Molecular Biology

M2 Macrophage Derived Extracellular Vesicle-Mediated Transfer of MiR-186-5p Promotes Colon Cancer Progression by Targeting DLC1

Junfeng Guo et al.

Summary: This study reveals the molecular mechanisms of M2 macrophage-derived extracellular vesicles (M2-EVs) in promoting colon cancer, with miR-186-5p identified as a key effector. It is found that M2-EVs transport miR-186-5p to inhibit DLC1 expression and activate the β-catenin pathway, leading to enhanced proliferation and motility of colon cancer cells.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2022)

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Article Engineering, Biomedical

Targeted immunomodulation therapy for cardiac repair by platelet membrane engineering extracellular vesicles via hitching peripheral monocytes

Qiyu Li et al.

Summary: The study found that by modifying the surface membrane of extracellular vesicles, the targeting ability of the vesicles can be improved, promoting the reprogramming of macrophages and ultimately regulating the immune microenvironment to achieve cardiac repair.

BIOMATERIALS (2022)

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Article Cell & Tissue Engineering

Characterization and bioassays of extracellular vesicles extracted by tangential flow filtration

Xiaoli Zeng et al.

Summary: In this study, it was found that extracellular vesicles isolated from stem cell supernatants using the ultrafiltration method displayed similar cell proliferation ability compared to the traditional method. Furthermore, the yield and anti-aging capability of the vesicles were significantly increased. Therefore, this scalable and effective isolation method has the potential to facilitate the clinical use of vesicles.

REGENERATIVE MEDICINE (2022)

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Article Engineering, Biomedical

Functional siRNA Delivery by Extracellular Vesicle-Liposome Hybrid Nanoparticles

Martijn J. W. Evers et al.

Summary: EV-liposome hybrid nanoparticles have been investigated as a potential siRNA delivery system, demonstrating their ability to encapsulate siRNA, contain EV-surface markers, and functionally deliver siRNA to different cell types. These hybrids combine the benefits of both synthetic and biological drug delivery systems, showing altered functional behavior compared to liposomes and varying efficacy among recipient cell types.

ADVANCED HEALTHCARE MATERIALS (2022)

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Article Pharmacology & Pharmacy

Extracellular Vesicles from M1-Polarized Macrophages Combined with Hyaluronic Acid and a beta-Blocker Potentiate Doxorubicin's Antitumor Activity by Downregulating Tumor-Associated Macrophages in Breast Cancer

Carla Jorquera-Cordero et al.

Summary: The immunosuppressive tumor microenvironment is one of the main reasons for the low response of cancer to chemotherapy. The study found that modified extracellular vesicles produced by macrophages can enhance the anti-tumor effects and alter the tumor microenvironment. This method can effectively reduce tumor size and metastasis, and promote cell apoptosis.

PHARMACEUTICS (2022)

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Review Biochemistry & Molecular Biology

Macrophage-Derived Extracellular Vesicles: A Promising Tool for Personalized Cancer Therapy

Antonella Barone et al.

Summary: The incidence of cancer is increasing significantly and the lack of efficacy in cancer therapies can be attributed to various factors such as delayed diagnosis, tumor regrowth, and multidrug resistance. Macrophages play a crucial role in tumor suppression or progression, and macrophage-derived extracellular vesicles (EVs) are important mediators in the tumor microenvironment. Their ability to facilitate cell-cell and organ-cell communication by delivering nucleic acids and proteins makes them potential targets for personalized anticancer nanomedicine.

BIOMEDICINES (2022)

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Review Oncology

The Potential Role of Exosomal Proteins in Prostate Cancer

Shangzhi Feng et al.

Summary: Prostate cancer is the most common malignant tumor in men in developed countries. Traditional diagnostic and therapeutic methods are no longer suitable, and finding new markers and targets has become a hot topic. Exosomes, small vesicles with a regulatory role in cancer development, have been extensively studied. However, there is a lack of systematic review on the role of exosomal proteins in prostate cancer.

FRONTIERS IN ONCOLOGY (2022)

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Article Biochemistry & Molecular Biology

Exploration and functionalization of M1-macrophage extracellular vesicles for effective accumulation in glioblastoma and strong synergistic therapeutic effects

Xiaojun Wang et al.

Summary: The researchers successfully developed M1-like macrophage-derived extracellular vesicles (M1EVs) for the treatment of glioblastoma multiforme (GBM). These M1EVs achieved synergistic immunomodulation, chemiexcited photodynamic therapy (CDT), and hypoxia-activated chemotherapy in GBM, leading to a potent therapeutic effect. The results demonstrated the excellent efficacy of CCA-M1EVs against GBM in cell-derived and patient-derived xenograft models.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

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Article Engineering, Biomedical

Peptide-guided resiquimod-loaded lignin nanoparticles convert tumor-associated macrophages from M2 to M1 phenotype for enhanced chemotherapy

Patricia Figueiredo et al.

Summary: Nanomedicines are innovative technologies that improve the therapeutic effects of drugs for cancer treatment by targeting M2-like tumor-associated macrophages and modulating the tumor microenvironment.

ACTA BIOMATERIALIA (2021)

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Editorial Material Cell Biology

M2 macrophage-derived extracellular vesicles facilitate CD8+T cell exhaustion in hepatocellular carcinoma via the miR-21-5p/YOD1/YAP/β-catenin pathway

Jian Pu et al.

Summary: This study revealed that M2 macrophage-derived extracellular vesicles facilitated CD8(+) T cell exhaustion in HCC patients through the miR-21-5p/YOD1/YAP/beta-catenin axis. Inhibition of miR-21-5p or overexpression of YOD1 could annul the promoting effect of EVs on CD8(+) T cell exhaustion.

CELL DEATH DISCOVERY (2021)

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Article Engineering, Biomedical

An efficient photochemotherapy nanoplatform based on the endogenous biosynthesis of photosensitizer in macrophage-derived extracellular vesicles

Ruomeng Li et al.

Summary: Extracellular vesicles (EVs) have been developed as promising drug delivery vehicles due to their biocompatibility and long-term circulation. This study presents a simple and effective method for in situ biosynthesis of tumor-targeting EVs with high drug-loading efficiency, showing great potential for reliable photochemotherapy in biomedicine applications.

BIOMATERIALS (2021)

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Article Engineering, Biomedical

Macrophage-derived implantable vaccine prevents postsurgical tumor recurrence

Dongqing Wang et al.

Summary: Immunotherapy is a potential therapeutic strategy against tumor relapse, but the immunosuppressive tumor microenvironment is a barrier. Re-educating tumor-associated macrophages (TAMs) is critical for improving the efficacy of immunotherapy. An engineered macrophage-derived implantable vaccine can prevent postsurgical tumor relapse and reduce lung metastasis by inducing a shift in macrophage polarization and stimulating systemic immunity.

BIOMATERIALS (2021)

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Article Biophysics

Legumain protease-activated tuftsin-functionalized nanoparticles for dual-targeting TAMs and cancer chemotherapy

Hui Peng et al.

Summary: In this study, a novel dual-targeting nanoparticle system for TAMs and tumor cells was developed for cancer chemotherapy. The system can be activated to promote tumor cells internalization and TAMs phagocytosis, leading to enhanced efficacy against tumor growth and TAMs depletion.

COLLOIDS AND SURFACES B-BIOINTERFACES (2021)

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Article Immunology

Therapeutic and prophylactic effects of macrophage-derived small extracellular vesicles in the attenuation of inflammatory pain

Renee Jean-Toussaint et al.

Summary: sEVs derived from macrophages contain anti-inflammatory miRNAs that can reduce inflammation and pain responses. By being taken up by neurons, microglia, and astrocytes, sEVs lead to downregulation of proinflammatory miRNA target genes, alleviating pain and modulating immune pathways.

BRAIN BEHAVIOR AND IMMUNITY (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Article Biotechnology & Applied Microbiology

M2 Macrophage-Derived Exosomes Promote Angiogenesis and Growth of Pancreatic Ductal Adenocarcinoma by Targeting E2F2

Yuhan Yang et al.

Summary: The study revealed that exosomes derived from M2 macrophages can promote angiogenesis in PDAC, leading to accelerated tumor growth. By transferring miR-155-5p and miR-221-5p to endothelial cells, the interaction between TAMs and angiogenesis in PDAC was further confirmed. Targeting exosomal miRNAs from TAMs may provide diagnostic and therapeutic strategies for PDAC.

MOLECULAR THERAPY (2021)

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Review Engineering, Biomedical

Smart transformable nanomedicines for cancer therapy

Yuequan Wang et al.

Summary: Significant progress has been made in nanoparticulate drug delivery systems, but there are still multiple delivery dilemmas impairing the efficiency of nanomedicines. Smart transformable nanomedicines based on in vivo drug delivery process are promising for overcoming these delivery obstacles. Efforts have been devoted to developing smart transformable anticancer nanomedicines, including size-reducible nanoparticles, transformable nanostructures, and shell-detachable nanocarriers.

BIOMATERIALS (2021)

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Article Multidisciplinary Sciences

Mitochondrial ATP fuels ABC transporter-mediated drug efflux in cancer chemoresistance

Emily L. Giddings et al.

Summary: Chemotherapy is the standard treatment for most cancers worldwide, but chemoresistance due to ABC transporters is a significant challenge. The study highlights the role of mitochondrial respiration in supplying ATP for ABC transporters, and how inhibiting mitochondrial respiration can overcome chemoresistance. Development of MCJ mimetics offers a potential alternative strategy for treating multiple cancers by targeting this mechanism.

NATURE COMMUNICATIONS (2021)

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Article Engineering, Biomedical

Gene-engineered exosomes-thermosensitive liposomes hybrid nanovesicles by the blockade of CD47 signal for combined photothermal therapy and cancer immunotherapy

Lili Cheng et al.

Summary: The designed hybrid therapeutic nanovesicles, hGLV, based on CD47 immune checkpoint blockade demonstrated long blood circulation, improved macrophage-mediated phagocytosis of tumor cells by blocking CD47 signal, targeted homologous tumors in mice effectively for preferential accumulation at tumor sites. Furthermore, hGLV loaded with photothermal agent achieved excellent photothermal therapy (PTT) in eliminating tumors, inducing immunogenic cell death, generating tumor-associated antigens, and promoting immune responses with the help of co-encapsulated immune adjuvant. Such hybrid nanovesicles show promise in drug delivery for cancer treatment.

BIOMATERIALS (2021)

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Article Pharmacology & Pharmacy

M1 Macrophage-Derived Exosomes Loaded with Gemcitabine and Deferasirox against Chemoresistant Pancreatic Cancer

Yongmei Zhao et al.

Summary: This study developed a specific drug delivery system based on M1 macrophage-derived exosomes for pancreatic cancer with chemoresistance. The nanoformulation combining GEM and DFX in M1Exo significantly enhanced therapeutic efficacy against GEM-resistant cancer cells.

PHARMACEUTICS (2021)

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Article Medicine, Research & Experimental

CircUbe3a from M2 macrophage-derived small extracellular vesicles mediates myocardial fibrosis after acute myocardial infarction

Yan Wang et al.

Summary: The study revealed that M2M-derived circUbe3a-containing SEVs promote the proliferation, migration, and phenotypic transformation of CFs by directly targeting the miR-138-5p/RhoC axis, exacerbating myocardial fibrosis.

THERANOSTICS (2021)

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Review Biochemistry & Molecular Biology

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

He-Ming Zhou et al.

Summary: Understanding the key characteristics and resistance mechanisms of CSCs may improve patient outcomes and reduce relapse. Targeting the mechanisms and pathways of CSCs described in this review could lead to further drug discovery and therapy development.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Medicine, Research & Experimental

Engineering exosomes for targeted drug delivery

Yujie Liang et al.

Summary: Exosomes can be engineered through genetic and chemical methods for targeted drug delivery, increasing the local concentration of therapeutics and minimizing side effects.

THERANOSTICS (2021)

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Macrophage-Derived Extracellular Vesicles as Drug Delivery Systems for Triple Negative Breast Cancer (TNBC) Therapy

Matthew J. Haney et al.

JOURNAL OF NEUROIMMUNE PHARMACOLOGY (2020)

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Antitumor efficacy of interferon-γ-modified exosomal vaccine in prostate cancer

Xiaojun Shi et al.

PROSTATE (2020)

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The roles of tumor-associated macrophages in tumor angiogenesis and metastasis

Luo-Qin Fu et al.

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Thermosensitive Exosome-Liposome Hybrid Nanoparticle-Mediated Chemoimmunotherapy for Improved Treatment of Metastatic Peritoneal Cancer

Qijun Lv et al.

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The tumor microenvironment

Nicole M. Anderson et al.

CURRENT BIOLOGY (2020)

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Analysis of RNA yield in extracellular vesicles isolated by membrane affinity column and differential ultracentrifugation

Gilberto Gutierrez Garcia et al.

PLOS ONE (2020)

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Review Cell Biology

Macrophage-derived extracellular vesicles: diverse mediators of pathology and therapeutics in multiple diseases

Yizhuo Wang et al.

CELL DEATH & DISEASE (2020)

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Proinflammatory macrophage-derived microvesicles exhibit tumor tropism dependent on CCL2/CCR2 signaling axis and promote drug delivery via SNARE-mediated membrane fusion

Ling Guo et al.

THERANOSTICS (2020)

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Sha Li et al.

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The importance of extracellular vesicle purification for downstream analysis: A comparison of differential centrifugation and size exclusion chromatography for helminth pathogens

Chelsea N. Davis et al.

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Macrophage-derived exosome-mimetic hybrid vesicles for tumor targeted drug delivery

Sagar Rayamajhi et al.

ACTA BIOMATERIALIA (2019)

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Molecular Profiling and Functional Analysis of Macrophage-Derived Tumor Extracellular Vesicles

Chiara Cianciaruso et al.

CELL REPORTS (2019)

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The multi-factorial nature of clinical multidrug resistance in cancer

Yehuda G. Assaraf et al.

DRUG RESISTANCE UPDATES (2019)

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Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy

Chunai Gong et al.

JOURNAL OF NANOBIOTECHNOLOGY (2019)

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Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research

Sohee Moon et al.

JOURNAL OF CLINICAL MEDICINE (2019)

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Exosomes from M1-Polarized Macrophages Enhance Paclitaxel Antitumor Activity by Activating Macrophages-Mediated Inflammation

Piaopiao Wang et al.

THERANOSTICS (2019)

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Tumor-associated macrophages: an accomplice in solid tumor progression

Yibing Chen et al.

JOURNAL OF BIOMEDICAL SCIENCE (2019)

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Macrophages as regulators of tumour immunity and immunotherapy

David G. DeNardo et al.

NATURE REVIEWS IMMUNOLOGY (2019)

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Review Biochemistry & Molecular Biology

Extracellular vesicle isolation methods: rising impact of size-exclusion chromatography

Marta Monguio-Tortajada et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2019)

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Metabolic Regulation of Macrophage Polarization in Cancer

Kamiya Mehla et al.

TRENDS IN CANCER (2019)

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Methotrexate-Loaded Extracellular Vesicles Functionalized with Therapeutic and Targeted Peptides for the Treatment of Glioblastoma Multiforme

Zhilan Ye et al.

ACS APPLIED MATERIALS & INTERFACES (2018)

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Engineering Extracellular Vesicles with the Tools of Enzyme Prodrug Therapy

Gregor Fuhrmann et al.

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Carmen Belli et al.

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Hiroshi Kubo

CHEST (2018)

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Engineering macrophage-derived exosomes for targeted paclitaxel delivery to pulmonary metastases: in vitro and in vivo evaluations

Myung Soo Kim et al.

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2018)

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CURRENT DRUG DELIVERY (2018)

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M1 Macrophage-Derived Nanovesicles Potentiate the Anticancer Efficacy of Immune Checkpoint Inhibitors

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Nanoparticles as carriers for drug delivery in cancer

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ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY (2018)

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Analyses of repeated failures in cancer therapy for solid tumors: poor tumor-selective drug delivery, low therapeutic efficacy and unsustainable costs

Hiroshi Maeda et al.

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Enrichment of extracellular vesicles from human synovial fluid using size exclusion chromatography

Andrew D. Foers et al.

JOURNAL OF EXTRACELLULAR VESICLES (2018)

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Exosomes from M1-Polarized Macrophages Potentiate the Cancer Vaccine by Creating a Pro-inflammatory Microenvironment in the Lymph Node

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MOLECULAR THERAPY (2017)

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Polymer-based precipitation preserves biological activities of extracellular vesicles from an endometrial cell line

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BIOMATERIALS (2017)

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New methods in the diagnosis of cancer and gene therapy of cancer based on nanoparticles

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Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy

Yoshihiro Komohara et al.

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Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells

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NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2016)

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Dual inhibition of Ang-2 and VEGF receptors normalizes tumor vasculature and prolongs survival in glioblastoma by altering macrophages

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug

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NATURE COMMUNICATIONS (2015)

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Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies

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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS (2014)

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CANCER CELL (2014)

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Tumor-Associated Macrophages: From Mechanisms to Therapy (vol 41, pg 49, 2014)

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IMMUNITY (2014)

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Functional significance of macrophage-derived exosomes in inflammation and pain

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Tracking of intertissue migration reveals the origins of tumor-infiltrating monocytes

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

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Tissue-Resident Macrophages Self-Maintain Locally throughout Adult Life with Minimal Contribution from Circulating Monocytes

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