scholarly journals An Update on Novel Therapeutic Warfronts of Extracellular Vesicles (EVs) in Cancer Treatment: Where We Are Standing Right Now and Where to Go in the Future

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Zerwa Siddique ◽  
Amin Arif ◽  
Nadeem Sheikh
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Clinical Applications ◽  
Pathological Conditions ◽  
Potential Biomarker ◽  
Wide Range ◽  
Intercellular Communications ◽  
Multiple Stages ◽  
Novel Therapeutic

Extracellular vesicles (EVs) are a heterogeneous group of membrane-bounded vesicles that are believed to be produced and secreted by presumably all cell types under physiological and pathological conditions, including tumors. EVs are very important vehicles in intercellular communications for both shorter and longer distances and are able to deliver a wide range of cargos including proteins, lipids, and various species of nucleic acids effectively. EVs have been emerging as a novel biotherapeutic platform to efficiently deliver therapeutic cargos to treat a broad range of diseases including cancer. This vast potential of drug delivery lies in their abilities to carry a variety of cargos and their ease in crossing the biological membranes. Similarly, their presence in a variety of body fluids makes them a potential biomarker for early diagnosis, prognostication, and surveillance of cancer. Here, we discuss the relatively least and understudied aspects of EV biology and tried to highlight the obstacles and limitations in their clinical applications and also described most of the new warfronts to beat cancer at multiple stages. However, much more challenges still remain to evaluate EV-based therapeutics, and we are very much hopeful that the current work prompts further discovery.

scholarly journals Extracellular vesicles from dHL-60 cells as delivery vehicles for diverse therapeutics

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jun-Kyu Kim ◽  
Young-Jin Youn ◽  
Yu-Bin Lee ◽  
Sun-Hwa Kim ◽  
Dong-Keun Song ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Macrophage Polarization ◽  
Promyelocytic Leukemia ◽  
Leukemia Cells ◽  
Effector Functions ◽  
Potential Source ◽  
Monocyte Chemotaxis ◽  
Delivery Vehicles ◽  
Intercellular Communications

AbstractExtracellular vesicles (EVs) are membrane-derived heterogeneous vesicles that mediate intercellular communications. They have recently been considered as ideal vehicles for drug-delivery systems, and immune cells are suggested as a potential source for drug-loaded EVs. In this study, we investigated the possibility of neutrophils as a source for drug-loaded EVs. Neutrophil-like differentiated human promyelocytic leukemia cells (dHL-60) produced massive amounts of EVs within 1 h. The dHL-60 cells are also easily loaded with various cargoes such as antibiotics (penicillin), anticancer drug (paclitaxel), chemoattractant (MCP-1), miRNA, and Cas9. The EVs derived from the dHL-60 cells showed efficient incorporation of these cargoes and significant effector functions, such as bactericidal activity, monocyte chemotaxis, and macrophage polarization. Our results suggest that neutrophils or neutrophil-like promyelocytic cells could be an attractive source for drug-delivery EVs.

scholarly journals Extracellular Vesicles-Based Drug Delivery Systems: A New Challenge and the Exemplum of Malignant Pleural Mesothelioma

2020 ◽  
Vol 21 (15) ◽  
pp. 5432 ◽  
Author(s):  
Stefano Burgio ◽  
Leila Noori ◽  
Antonella Marino Gammazza ◽  
Claudia Campanella ◽  
Mariantonia Logozzi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Early Diagnosis ◽  
Extracellular Vesicles ◽  
Delivery System ◽  
Malignant Pleural Mesothelioma ◽  
Cell Communication ◽  
Cell Types ◽  
Delivery Systems ◽  
Pleural Mesothelioma ◽  
Potential Use

Research for the most selective drug delivery to tumors represents a fascinating key target in science. Alongside the artificial delivery systems identified in the last decades (e.g., liposomes), a family of natural extracellular vesicles (EVs) has gained increasing focus for their potential use in delivering anticancer compounds. EVs are released by all cell types to mediate cell-to-cell communication both at the paracrine and the systemic levels, suggesting a role for them as an ideal nano-delivery system. Malignant pleural mesothelioma (MPM) stands out among currently untreatable tumors, also due to the difficulties in achieving an early diagnosis. Thus, early diagnosis and treatment of MPM are both unmet clinical needs. This review looks at indirect and direct evidence that EVs may represent both a new tool for allowing an early diagnosis of MPM and a potential new delivery system for more efficient therapeutic strategies. Since MPM is a relatively rare malignant tumor and preclinical MPM models developed to date are very few and not reliable, this review will report data obtained in other tumor types, suggesting the potential use of EVs in mesothelioma patients as well.

scholarly journals Exosomal Heat Shock Proteins as New Players in Tumour Cell-to-Cell Communication

2014 ◽  
Vol 3 (1) ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Antonella Marino Gammazza ◽  
Dragana Nikolic ◽  
Francesca Rappa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Cell Communication ◽  
Clinical Applications ◽  
Cancer Development ◽  
Pathological Conditions ◽  
Key Players ◽  
Novel Biomarkers ◽  
Shock Proteins

Exosomes have recently been proposed as novel elements in the study of intercellular communication in normal and pathological conditions. The biomolecular composition of exosomes reflects the specialized functions of the original cells. Heat shock proteins (Hsps) are a group of chaperone proteins with diverse biological roles. In recent years, many studies have focused on the extracellular roles played by Hsps that appear to be involved in cancer development and immune system stimulation. Hsps localized on the surface of exosomes, secreted by normal and tumour cells, could be key players in intercellular cross-talk, particularly during the course of different diseases, such as cancer. Exosomal Hsps offer significant opportunities for clinical applications, including their use as potential novel biomarkers for the diagnoses or prognoses of different diseases, or for therapeutic applications and drug delivery.

scholarly journals Emerging role of extracellular vesicles in liver diseases

2019 ◽  
Vol 317 (5) ◽  
pp. G739-G749 ◽  
Author(s):  
Harmeet Malhi
Keyword(s):  
Extracellular Vesicles ◽  
Cell Communication ◽  
Cell Types ◽  
Cell Responses ◽  
Therapeutic Delivery ◽  
Disease States ◽  
Therapeutic Uses ◽  
Potential Biomarker ◽  
Secretion Pathways

Extracellular vesicles (EVs) are membrane-defined nanoparticles released by most cell types. The EVs released by cells may differ quantitatively and qualitatively from physiological states to disease states. There are several unique properties of EVs, including their proteins, lipids and nucleic acid cargoes, stability in circulation, and presence in biofluids, which make them a critical vector for cell-to-cell communication and impart utility as a biomarker. EVs may also serve as a vehicle for selective cargo secretion. Similarly, EV cargo may be selectively manipulated for targeted therapeutic delivery. In this review an overview is provided on the EV classification, biogenesis, and secretion pathways, which are conserved across cell types. Next, cargo characterization and effector cell responses are discussed in the context of nonalcoholic steatohepatitis, alcoholic hepatitis, and acetaminophen-induced liver injury. The review also discusses the potential biomarker and therapeutic uses of circulating EVs.

scholarly journals Milk-Derived Extracellular Vesicles in Inter-Organism, Cross-Species Communication and Drug Delivery

Proteomes ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 11 ◽  
Author(s):  
Rahul Sanwlani ◽  
Pamali Fonseka ◽  
Sai V. Chitti ◽  
Suresh Mathivanan
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Immune Modulation ◽  
Cell Types ◽  
Economic Viability ◽  
Peripheral Tissues ◽  
Disease Therapy ◽  
Significant Interest ◽  
Immunologic Reactions

Milk is considered as more than a source of nutrition for infants and is a vector involved in the transfer of bioactive compounds and cells. Milk contains abundant quantities of extracellular vesicles (EVs) that may originate from multiple cellular sources. These nanosized vesicles have been well characterized and are known to carry a diverse cargo of proteins, nucleic acids, lipids and other biomolecules. Milk-derived EVs have been demonstrated to survive harsh and degrading conditions in gut, taken up by various cell types, cross biological barriers and reach peripheral tissues. The cargo carried by these dietary EVs has been suggested to have a role in cell growth, development, immune modulation and regulation. Hence, there is considerable interest in understanding the role of milk-derived EVs in mediating inter-organismal and cross-species communication. Furthermore, various attributes such as it being a natural source, as well as its abundance, scalability, economic viability and lack of unwarranted immunologic reactions, has generated significant interest in deploying milk-derived EVs for clinical applications such as drug delivery and disease therapy. In this review, the role of milk-derived EVs in inter-organismal, cross-species communication and in drug delivery is discussed.

scholarly journals Skeletal muscle releases extracellular vesicles with distinct protein and miRNA signatures that accumulate and function within the muscle microenvironment

2021 ◽  
Author(s):  
Sho Watanabe ◽  
Yuri Sudo ◽  
Satoshi Kimura ◽  
Kenji Tomita ◽  
Makoto Noguchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
The Body ◽  
C2c12 Cells ◽  
Ips Cell ◽  
Potential Marker ◽  
And Function ◽  
Intercellular Communications

Extracellular vesicles (EVs) contain various regulatory molecules and mediate intercellular communications. Although EVs are secreted from various cell types, including skeletal muscle cells, and present in the blood, their identity is poorly characterized in vivo, limiting the identification of their origin in the blood. Since the skeletal muscle is the largest organ in the body, it could substantially contribute to circulating EVs as their source. However, due to the lack of defined markers that distinguish SkM-EVs from others, whether the skeletal muscle releases EVs in vivo and how much the skeletal muscle-derived EVs (SkM-EVs) account for plasma EVs remain poorly understood. In this work, we perform quantitative proteomic analyses on EVs released from C2C12 cells and human iPS cell-derived myocytes and identify potential marker proteins that mark SkM-EVs. These markers we identified apply to in vivo tracking of SkM-EVs. The results show that skeletal muscle makes only a subtle contribution to plasma EVs as their source in both control and exercise conditions in mice. On the other hand, we demonstrate that SkM-EVs are concentrated in the skeletal muscle interstitium. Furthermore, we show that interstitium EVs are highly enriched with the muscle-specific miRNAs and repress the expression of the paired box transcription factor Pax7, a master regulator for myogenesis. Taken together, our findings reveal that the skeletal muscle releases exosome-like small EVs with distinct protein and miRNA profiles in vivo and that SkM-EVs mainly play a role within the muscle microenvironment where they accumulate.

scholarly journals Extracellular vesicles therapy: opportunities, mechanisms and perspectives

2020 ◽  
Vol 25 (10) ◽  
pp. 4081
Author(s):  
F. S. Velikonivtsev ◽  
A. S. Golovkin
Keyword(s):  
Extracellular Vesicles ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Biological Membrane ◽  
Biologically Active ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Clinical Conditions ◽  
Intercellular Communications

Extracellular vesicles are biological membrane-coated objects with size less then 1000 nm. They can contain variety of biologically active molecules (such as proteins, miRNA, mRNA, DNA etc.) and also are able to provide intercellular communications and implement lots if biological functions. Now possibilities of using extracellular vesicles for therapeutic approaches against various diseases and pathological conditions are rapidly discovered. In the most of cases mesenchymal stem cells are the sources of extracellular vesicles and miRNAs which vesicles transport are considered to be causable agents of their activities. In-vitro studies show that extracellular vesicles provide anti-inflammatory, anti-apoptotic activities and can stimulate angiogenesis and regeneration. Performed studies which were analyzed and structurized by us in this review demonstrate current perspectives for clinical use of extracellular vesicles in the therapy of such clinical conditions as oxidative stress, ischemia-reperfusion injury, tumor growth etc.

scholarly journals Recent Advances in Extracellular Vesicles as Drug Delivery Systems and Their Potential in Precision Medicine

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1006 ◽  
Author(s):  
Bart de Jong ◽  
Eric Raul Barros ◽  
Joost G. J. Hoenderop ◽  
Juan Pablo Rigalli
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Current Knowledge ◽  
Early Stage ◽  
Treatment Options ◽  
Cell Types ◽  
Administration Routes ◽  
The Individual ◽  
Key Steps

Extracellular vesicles (EVs) are membrane-bilayered nanoparticles released by most cell types. Recently, an enormous number of studies have been published on the potential of EVs as carriers of therapeutic agents. In contrast to systems such as liposomes, EVs exhibit less immunogenicity and higher engineering potential. Here, we review the most relevant publications addressing the potential and use of EVs as a drug delivery system (DDS). The information is divided based on the key steps for designing an EV-mediated delivery strategy. We discuss possible sources and isolation methods of EVs. We address the administration routes that have been tested in vivo and the tissue distribution observed. We describe the current knowledge on EV clearance, a significant challenge towards enhancing bioavailability. Also, EV-engineering approaches are described as alternatives to improve tissue and cell-specificity. Finally, a summary of the ongoing clinical trials is performed. Although the application of EVs in the clinical practice is still at an early stage, a high number of studies in animals support their potential as DDS. Thus, better treatment options could be designed to precisely increase target specificity and therapeutic efficacy while reducing off-target effects and toxicity according to the individual requirements of each patient.

A pH-triggered fluorescence-switchable extracellular vesicle for tracing drug release and improving drug delivery

2021 ◽  
Author(s):  
Shaobing Zhou ◽  
Rui Su ◽  
Xiang Xiong ◽  
Yingping Li ◽  
Xiaoqing Wei ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Extracellular Vesicles ◽  
Extracellular Vesicle ◽  
Clinical Applications ◽  
Clinical Translation ◽  
On Demand

Extracellular vesicles have shown great potential in drug delivery for clinical applications. However, some obstacles are still needed to be overcome before their clinical translation, including on demand release of...

scholarly journals Bioinspired Extracellular Vesicles: Lessons Learned From Nature for Biomedicine and Bioengineering

Nanomaterials ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2172 ◽  
Author(s):  
Assaf Zinger ◽  
Ava Brozovich ◽  
Anna Pasto ◽  
Manuela Sushnitha ◽  
Jonathan O. Martinez ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Nucleic Acids ◽  
Structure Function ◽  
Small Molecules ◽  
Extracellular Vesicles ◽  
Clinical Applications ◽  
Lessons Learned ◽  
Efficient Communication ◽  
Exchange Information ◽  
Cell Carriers

Efficient communication is essential in all layers of the biological chain. Cells exchange information using a variety of signaling moieties, such as small molecules, proteins, and nucleic acids. Cells carefully package these messages into lipid complexes, collectively named extracellular vesicles (EVs). In this work, we discuss the nature of these cell carriers, categorize them by their origin, explore their role in the homeostasis of healthy tissues, and examine how they regulate the pathophysiology of several diseases. This review will also address the limitations of using EVs for clinical applications and discuss novel methods to engineer nanoparticles to mimic the structure, function, and features of EVs. Using lessons learned from nature and understanding how cells use EVs to communicate across distant sites, we can develop a better understanding of how to tailor the fundamental features of drug delivery carriers to encapsulate various cargos and target specific sites for biomedicine and bioengineering.

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