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Extracellular Vesicles as Drug Targets and Delivery Vehicles for Cancer Therapy

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Summary: Extracellular vesicles (EVs) have the potential to overcome limitations in clinical use of chemotherapeutics. By optimizing the electroporation technique, drugs can be efficiently loaded into EVs, leading to improved drug transport efficacy and therapeutic potency with reduced adverse effects.

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Summary: Mesenchymal stem cells (MSCs) have paracrine effects in therapy, and extracellular vesicles (EVs) play a crucial role in intercellular communication. MSC-EVs have potential therapeutic applications and play an important role in fibrosis treatment and tissue repair.

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Application of engineered extracellular vesicles for targeted tumor therapy

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Summary: All cells can release extracellular vesicles (EVs) containing various cellular components, which are crucial for intercellular communication and maintaining internal homeostasis. EVs have shown great potential in drug delivery and precision therapy due to their targeting specificity and regulatory ability. They can modulate immune system function by influencing the tumor microenvironment and can be combined with other delivery systems to enhance drug delivery efficiency.

JOURNAL OF BIOMEDICAL SCIENCE (2022)

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Milk exosomes: A biogenic nanocarrier for small molecules and macromolecules to combat cancer

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Summary: Exosomes are biogenic nanocarriers of endocytic origin found in biofluids like milk, with milk exosomes being a particularly promising source for drug delivery. They are being increasingly explored for delivering both small drug molecules and siRNA to combat cancer, thanks to their biocompatibility and unique properties. Various isolation techniques, physicochemical properties, biodistribution, and applications of milk exosomes in drug delivery were highlighted in this article.

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY (2021)

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High-quality milk exosomes as oral drug delivery system

Jie Zhong et al.

Summary: Exosomes are nano-sized extracellular vesicles secreted by mammalian cells, including milk exosomes which have the potential to cross biological barriers and serve as promising drug delivery tools for oral administration.

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Exosomal miRNA as peripheral biomarkers in Parkinson's disease and progressive supranuclear palsy: A pilot study

Ida Manna et al.

Summary: This study demonstrated the potential of exosomal miRNAs as biomarkers to differentiate between Parkinson's disease and Progressive Supranuclear Paralysis, with specific miRNAs like miR-21-3p, miR-22-3p, miR-223-5p, miR-425-5p, miR-21-3p, and miR-199a-5p showing promise in accurate discrimination. The classifier consisting of six exosomal miRNAs had high diagnostic sensitivity and specificity in distinguishing PSP from PD.

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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.

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Factors Affecting Extracellular Vesicles Based Drug Delivery Systems

Isha Gaurav et al.

Summary: This review summarizes recent studies on the development of EV-based DDS and its advantages compared to conventional NDDS. It compares liposomes and exosomes in terms of their distinct benefits in DDS, analyzes considerations for better isolation and characterization of EVs for DDS, summarizes different methods for EV surface modification, discusses different origins of EVs and their role in developing DDS, includes major methods for encapsulating therapeutic cargos in EVs, and highlights key challenges and important open questions for further investigation in developing more effective EV-based DDS.

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Sulfisoxazole does not inhibit the secretion of small extracellular vesicles

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Overview and Update on Methods for Cargo Loading into Extracellular Vesicles

Yohan Han et al.

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Extracellular vesicles derived from oesophageal cancer containing P4HB promote muscle wasting via regulating PHGDH/Bcl-2/caspase-3 pathway

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JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Active cargo loading into extracellular vesicles: Highlights the heterogeneous encapsulation behaviour

Chaoxiang Chen et al.

Summary: Extracellular vesicles have unique advantages as nanocarriers for drug delivery, but their cargo encapsulation efficiency is often below expectations, especially for hydrophilic chemotherapeutic drugs. This study introduced a new method named SEAL, which significantly enhances drug encapsulation efficiency of EVs, and single-particle analysis techniques were used to uncover the encapsulation heterogeneity of EVs.

JOURNAL OF EXTRACELLULAR VESICLES (2021)

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Maria Chiara Ciferri et al.

Summary: Extracellular vesicles (EVs) are membrane-bound vesicles released by all cell types, playing a crucial role in intercellular communication and serving as biomarkers for various diseases. EVs isolated from stem/progenitor cells exhibit innate immunosuppressive and anti-inflammatory properties, making them potential vehicles for drug delivery.

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Extracellular vesicle- and particle-mediated communication shapes innate and adaptive immune responses

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Oral administration of bovine milk-derived extracellular vesicles induces senescence in the primary tumor but accelerates cancer metastasis

Monisha Samuel et al.

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NATURE COMMUNICATIONS (2021)

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Biodistribution of extracellular vesicles following administration into animals: A systematic review

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Extracellular vesicles-released parathyroid hormone-related protein from Lewis lung carcinoma induces lipolysis and adipose tissue browning in cancer cachexia

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Gemcitabine loaded autologous exosomes for effective and safe chemotherapy of pancreatic cancer

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Inhibition of Glioma Cells' Proliferation by Doxorubicin-Loaded Exosomes via Microfluidics

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Exosomal delivery of doxorubicin enables rapid cell entry and enhanced in vitro potency

Christina Schindler et al.

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Dennis K. Jeppesen et al.

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microRNA-21-5p dysregulation in exosomes derived from heart failure patients impairs regenerative potential

Li Qiao et al.

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Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma

Malgorzata Czystowska-Kuzmicz et al.

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Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques

Soodeh Salarpour et al.

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Extracellular Vesicles As Nanomedicine: Hopes And Hurdles In Clinical Translation

Thierry Burnouf et al.

INTERNATIONAL JOURNAL OF NANOMEDICINE (2019)

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A Nanodrug Consisting Of Doxorubicin And Exosome Derived From Mesenchymal Stem Cells For Osteosarcoma Treatment In Vitro

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Tumour exosomal CEMIP protein promotes cancer cell colonization in brain metastasis

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Aspirin-loaded nanoexosomes as cancer therapeutics

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Embryotrophic effects of extracellular vesicles derived from outgrowth embryos in pre- and peri-implantation embryonic development in mice

Jihyun Kim et al.

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Douglas V. Faget et al.

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Uchini S. Kosgodage et al.

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Extracellular vesicles as circulating cancer biomarkers: opportunities and challenges

R. E. Lane et al.

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Biocompatibility of highly purified bovine milk-derived extracellular vesicles

Masaharu Somiya et al.

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Annemiek Dickhout et al.

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Chloramidine/Bisindolylmaleimide-I-Mediated Inhibition of Exosome and Microvesicle Release and Enhanced Efficacy of Cancer Chemotherapy

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Milk-derived exosomes for oral delivery of paclitaxel

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Tumor induces muscle wasting in mice through releasing extracellular Hsp70 and Hsp90

Guohua Zhang et al.

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Small extracellular vesicles secreted from senescent cells promote cancer cell proliferation through EphA2

Masaki Takasugi et al.

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Malignant extracellular vesicles carrying MMP1 mRNA facilitate peritoneal dissemination in ovarian cancer

Akira Yokoi et al.

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Exosomes maintain cellular homeostasis by excreting harmful DNA from cells

Akiko Takahashi et al.

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Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin

Farrukh Aqil et al.

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Curcumin Encapsulated in Milk Exosomes Resists Human Digestion and Possesses Enhanced Intestinal Permeability in Vitro

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Exosomes expressing carbonic anhydrase 9 promote angiogenesis

Kengo Horie et al.

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Exosomal DNMT1 mediates cisplatin resistance in ovarian cancer

Ya-Lei Cao et al.

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Glioblastoma stem-like cells secrete the pro-angiogenic VEGF-A factor in extracellular vesicles

Lucas Treps et al.

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Engineering exosomes as refined biological nanoplatforms for drug delivery

Xin Luan et al.

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Hector Peinado et al.

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Pathogenesis of pancreatic cancer exosome-induced lipolysis in adipose tissue

Gunisha Sagar et al.

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Blood Exosomes Endowed with Magnetic and Targeting Properties for Cancer Therapy

Hongzhao Qi et al.

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Radha Munagala et al.

CANCER LETTERS (2016)

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Exosomal formulation enhances therapeutic response of celastrol against lung cancer

Farrukh Aqil et al.

EXPERIMENTAL AND MOLECULAR PATHOLOGY (2016)

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The biology and function of exosomes in cancer

Raghu Kalluri

JOURNAL OF CLINICAL INVESTIGATION (2016)

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Versatile roles of extracellular vesicles in cancer

Nobuyoshi Kosaka et al.

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

Myung Soo Kim et al.

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Pancreatic cancer-derived exosomes: new role in paraneoplastic syndromes?

Chi Lam Au Yeung et al.

TRANSLATIONAL CANCER RESEARCH (2016)

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Focus on Extracellular Vesicles: Introducing the Next Small Big Thing

Hina Kalra et al.

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Prostate cancer cells stimulated by calcium-mediated activation of protein kinase C undergo a refractory period before re-releasing calcium-bearing microvesicles

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Increased anti-tumour activity by exosomes derived from doxorubicin-treated tumour cells via heat stress

Yunshan Yang et al.

INTERNATIONAL JOURNAL OF HYPERTHERMIA (2015)

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Tumour exosome integrins determine organotropic metastasis

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NATURE (2015)

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The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

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NATURE (2015)

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Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver

Bruno Costa-Silva et al.

NATURE CELL BIOLOGY (2015)

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Exosome Delivered Anticancer Drugs Across the Blood-Brain Barrier for Brain Cancer Therapy in Danio Rerio

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PHARMACEUTICAL RESEARCH (2015)

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Pantethine Prevents Murine Systemic Sclerosis Through the Inhibition of Microparticle Shedding

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Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

Oscar P. B. Wiklander et al.

JOURNAL OF EXTRACELLULAR VESICLES (2015)

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Microvesicles containing miRNAs promote muscle cell death in cancer cachexia via TLR7

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

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Essential role for TrpC5-containing extracellular vesicles in breast cancer with chemotherapeutic resistance

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

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Exosomes reflect the hypoxic status of glioma cells and mediate hypoxia-dependent activation of vascular cells during tumor development

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

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NANOSCALE RESEARCH LETTERS (2013)

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Exosome removal as a therapeutic adjuvant in cancer

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Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET

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Secretory Mechanisms and Intercellular Transfer of MicroRNAs in Living Cells

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Rab27a and Rab27b control different steps of the exosome secretion pathway

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NATURE CELL BIOLOGY (2010)

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INTERNATIONAL JOURNAL OF CANCER (2009)

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Mesenchymal Stem Cell-Derived Microvesicles Protect Against Acute Tubular Injury

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JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY (2009)

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Senescence-associated exosome release from human prostate cancer cells

Brian D. Lehmann et al.

CANCER RESEARCH (2008)

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Protection against cerebral malaria by the low-molecular-weight thiol pantethine

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Ceramide triggers budding of exosome vesicles into multivesicular Endosomes

Katarina Trajkovic et al.

SCIENCE (2008)

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Mechanism of increased lipolysis in cancer cachexia

Thorhallur Agustsson et al.

CANCER RESEARCH (2007)

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A ROCK inhibitor permits survival of dissociated human embryonic stem cells

Kiichi Watanabe et al.

NATURE BIOTECHNOLOGY (2007)