scholarly journals Extracellular Vesicles and Their Interplay with Biological Membranes

2021 ◽  
Author(s):  
Jacob Yeo Xian Ping ◽  
Yub Raj Neupane ◽  
Giorgia Pastorin
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cells ◽  
Drug Delivery Systems ◽  
Biological Membranes ◽  
Drug Carriers ◽  
Biological Properties ◽  
Target Cells ◽  
Genetic Modifications ◽  
The Relationship ◽  
Extracellular Environment

Most cells secrete vesicles into the extracellular environment to interact with other cells. These extracellular vesicles (EVs), have undergone a paradigm shift upon the discovery that they also transport important material including proteins, lipids and nucleic acids. As natural cargo carriers, EVs are not recognised by the immune system as foreign substances, and consequently evade removal by immune cells. These intrinsic biological properties of EVs have led to further research on utilising EVs as potential diagnostic biomarkers and drug delivery systems (DDSs). However, the internalisation of EVs by target cells is still not fully understood. Moreover, it is unclear whether EVs can cross certain biological membranes like the blood-brain barrier (BBB) naturally, or require genetic modifications to do so. Hence, this review aims to evaluate the relationship between the composition of EVs and their association with different biological membranes they encounter before successfully releasing their cargo into target cells. This review identifies specific biomarkers detected in various EVs and important biological barriers present in the gastrointestinal, placental, immunological, neurological, lymphatic, pulmonary, renal and intracellular environments, and provides a recommendation on how to engineer EVs as potential drug carriers based on key proteins and lipids involved in crossing these barriers.

scholarly journals Extracellular Vesicles as Natural, Safe and Efficient Drug Delivery Systems

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 557 ◽  
Author(s):  
Federico Villa ◽  
Rodolfo Quarto ◽  
Roberta Tasso
Keyword(s):  
Extracellular Vesicles ◽  
Scientific Community ◽  
Drug Delivery Systems ◽  
Physiological Role ◽  
Quality Criteria ◽  
Drug Carriers ◽  
Cellular Communication ◽  
Biological Molecules ◽  
Therapeutic Molecules ◽  
Stringent Quality

Extracellular vesicles (EVs) are particles naturally released from cells, delimited by a lipid bilayer, carrying functionally active biological molecules. In addition to their physiological role in cellular communication, the interest of the scientific community has recently turned to the use of EVs as vehicles for delivering therapeutic molecules. Several attempts are being made to ameliorate drug encapsulation and targeting, but these efforts are thwarted if the starting material does not meet stringent quality criteria. Here, we take a step back to the sources and isolation procedures that could guarantee significant improvements in the purification of EVs to be used as drug carriers, highlighting the advantages and shortcomings of each approach.

scholarly journals Extracellular Vesicle- and Extracellular Vesicle Mimetics-Based Drug Delivery Systems: New Perspectives, Challenges, and Clinical Developments

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 442 ◽  
Author(s):  
Prakash Gangadaran ◽  
Byeong-Cheol Ahn
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Drug Carriers ◽  
Extracellular Vesicle ◽  
Native Structure ◽  
Advantages And Disadvantages ◽  
Intracellular Communication ◽  
Therapeutic Molecules ◽  
Organ Tropism

Extracellular vesicles (EVs) are small membrane-based nanovesicles naturally released from cells. Extracellular vesicles mimetics (EVMs) are artificial vesicles engineered from cells or in combination with lipid materials, and they mimic certain characteristics of EVs. As such, EVs facilitate intracellular communication by carrying and delivering biological materials, such as proteins, lipids, and nucleic acids, and they have been found to find organ tropism in preclinical studies. Because of their native structure and characteristics, they are considered promising drug carriers for future clinical use. This review outlines the origin and composition of natural EVs and EVM engineering and internalization. It then details different loading approaches, with examples of the drug delivery of therapeutic molecules. In addition, the advantages and disadvantages of loading drugs into EVs or EVMs as a drug delivery system are discussed. Finally, the advantages of EVMs over EVs and the future clinical translation of EVM-based drug delivery platforms are outlined.

scholarly journals Erythrocytes and Nanoparticles: New Therapeutic Systems

2021 ◽  
Vol 11 (5) ◽  
pp. 2173
Author(s):  
Clara Guido ◽  
Gabriele Maiorano ◽  
Carmen Gutiérrez-Millán ◽  
Barbara Cortese ◽  
Adriana Trapani ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Hybrid Approach ◽  
Drug Carriers ◽  
Delivery Systems ◽  
Target Cells ◽  
Preparation Methods ◽  
Medical Practitioners ◽  
Surface Receptors ◽  
Wide Range

Nano-delivery systems represent one of the most studied fields, thanks to the associated improvement in the treatment of human diseases. The functionality of nanostructures is a crucial point, which the effectiveness of nanodrugs depends on. A hybrid approach strategy using synthetic nanoparticles (NPs) and erythrocytes offers an optimal blend of natural and synthetic materials. This, in turn, allows medical practitioners to exploit the combined advantages of erythrocytes and NPs. Erythrocyte-based drug delivery systems have been investigated for their biocompatibility, as well as the long circulation time allowed by specific surface receptors that inhibit immune clearance. In this review, we will discuss several methods—whole erythrocytes as drug carriers, red blood cell membrane-camouflaged nanoparticles and nano-erythrosomes (NERs)—while paying attention to their application and specific preparation methods. The ability to target cells makes erythrocytes excellent drug delivery systems. They can carry a wide range of therapeutic molecules while also acting as bioreactors; thus, they have many applications in therapy and in the diagnosis of many diseases.

Novel biomarker and drug delivery systems for theranostics – extracellular vesicles

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ewa Ł. Stępień ◽  
Carina Rząca ◽  
Paweł Moskal
Keyword(s):  
Drug Delivery ◽  
Extracellular Vesicles ◽  
Drug Delivery Systems ◽  
Biological Fluids ◽  
Cell Types ◽  
Biological Properties ◽  
Delivery Systems ◽  
Cell Uptake ◽  
Positron Emission ◽  
Composition Structure

Abstract Extracellular vesicles (EVs) are nano- and micro-sized double-layered membrane entities derived from most cell types and released into biological fluids. Biological properties (cell-uptake, biocompatibility), and chemical (composition, structure) or physical (size, density) characteristics make EVs a good candidate for drug delivery systems (DDS). Recent advances in the field of EVs (e.g., scaling-up production, purification) and developments of new imaging methods (total-body positron emission tomography [PET]) revealed benefits of radiolabeled EVs in diagnostic and interventional medicine as a potential DDs in theranostics.

Exosomes: the ideal nanovectors for biodelivery

2013 ◽  
Vol 394 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Stefano Fais ◽  
Mariantonia Logozzi ◽  
Luana Lugini ◽  
Cristina Federici ◽  
Tommaso Azzarito ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Pathological Condition ◽  
Biological Properties ◽  
The Body ◽  
Target Cells ◽  
Positive Effects ◽  
Gender And Age ◽  
Infected Cells ◽  
Properties Of Materials ◽  
Potential Use

Abstract Nanomedicine aims to exploit the improved and often novel physical, chemical, and biological properties of materials at the nanometric scale, possibly with the highest level of biomimetism, an approach that simulates what occurs in nature. Although extracellularly released vesicles include both microvesicles (MVs) and exosomes, only exosomes have the size that may be considered suitable for potential use in nanomedicine. In fact, recent reports have shown that exosomes are able to interact with target cells within an organ or at a distance using different mechanisms. Much is yet to be understood about exosomes, and currently, we are looking at the visible top of an iceberg, with most of what we have to understand on these nanovesicles still under the sea. In fact, we know that exosomes released by normal cells always trigger positive effects, whereas those released by cells in pathological condition, such as tumor or infected cells, may induce undesired, dangerous, and mostly unknown effects, but we cannot exclude the possibility that exosomes may also be detrimental for the body in normal conditions. However, whether we consider extracellular vesicles as a whole, thus including MVs, it appears that even in normal conditions, extracellular vesicles may lead to unwanted effects, depending on gender and age. This review aims to critically emphasize existing data in the literature that support the possible roles of exosomes in both diagnostic and therapeutic scopes.

scholarly journals Stem Cell-Derived Extracellular Vesicles as Immunomodulatory Therapeutics

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yoojin Seo ◽  
Hyung-Sik Kim ◽  
In-Sun Hong
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cells ◽  
Bilayer Membrane ◽  
Target Cells ◽  
Membrane Structures ◽  
Paracrine Factors ◽  
Immune Effector ◽  
Effector Cells ◽  
Conventional Cell ◽  
And Migration

Mesenchymal stem cells (MSCs) have been reported to possess regulatory functions on immune cells which make them alternative therapeutics for the treatment of inflammatory and autoimmune diseases. The interaction between MSCs and immune cells through paracrine factors might be crucial for these immunomodulatory effects of MSCs. Extracellular vesicles (EVs) are defined as bilayer membrane structures including exosomes and microvesicles which contain bioactive paracrine molecules affecting the characteristics of target cells. Recently, several studies have revealed that EVs derived from MSCs (MSC-EVs) can reproduce similar therapeutic impacts of parent MSCs; MSC-EVs could regulate proliferation, maturation, polarization, and migration of various immune effector cells and modulate the immune microenvironment depending on the context by delivering inflammatory cytokines, transcription factors, and microRNAs. Therefore, MSC-EVs can be applied as novel and promising tools for the treatment of immune-related disorders to overcome the limitations of conventional cell therapy regarding efficacy and toxicity issues. In this review, we will discuss current insights regarding the major outcomes in the evaluation of MSC-EV function against inflammatory disease models, as well as immune cells.

scholarly journals The Role of Extracellular Vesicles: An Epigenetic View of the Cancer Microenvironment

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Zhongrun Qian ◽  
Qi Shen ◽  
Xi Yang ◽  
Yongming Qiu ◽  
Wenbin Zhang
Keyword(s):  
Extracellular Vesicles ◽  
Immune Cells ◽  
Posttranscriptional Regulation ◽  
Donor Cell ◽  
Cell Types ◽  
Cancer Microenvironment ◽  
Patients With Cancer ◽  
Proliferation And Metastasis ◽  
Extracellular Environment

Exosomes, microvesicles, and other extracellular vesicles are released by many cell types, including cancer cells and cancer-related immune cells. Extracellular vesicles can directly or indirectly facilitate the transfer of bioinformation to recipient cells or to the extracellular environment. In cancer, exosomes have been implicated in tumor initiation, proliferation, and metastasis. Extracellular vesicles can transmit proteins and nucleic acids that participate in DNA methylation, histone modification, and posttranscriptional regulation of RNA. Factors transmitted by extracellular vesicles reflect the donor cell status, and extracellular vesicles derived from tumor cells may be also responsible for altering expression of tumor promoting and tumor suppressing genes in recipient cells. Thus, circulating extracellular vesicles may act as biomarkers of cancer, and detection of these biomarkers may be applied to diagnosis or assessment of prognosis in patients with cancer.

scholarly journals Exo-D-MAPPS Attenuates Production of Inflammatory Cytokines and Promoted Generation of Immunosuppressive Phenotype in Peripheral Blood Mononuclear Cells

2019 ◽  
Vol 0 (0) ◽  
Author(s):  
Carl Randall Harrell ◽  
Bojana Simovic Markovic ◽  
Crissy Fellabaum ◽  
Dragica Miloradovic ◽  
Aleksandar Acovic ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Peripheral Blood Mononuclear Cells ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Biological Properties ◽  
Target Cells ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Mesenchymal stem cells (MSCs) produce immunomodulatory factors that regulate production of cytokines and chemokines in immune cells affecting their functional properties. Administration of MSCs-sourced secretome, including MSC-derived conditioned medium (MSC-CM) and MSC-derived exosomes (MSC-Exos), showed beneficial effects similar to those observed after transplantation of MSCs. Due to their nano-size dimension, MSC-Exos easily penetrate through the tissue and in paracrine and endocrine manner, may deliver MSC-sourced factors to the target immune cells modulating their function. MSCs derived from amniotic fluid (AF-MSCs) had superior cell biological properties than MSCs derived from bone marrow. We recently developed “Exosomes Derived Multiple Allogeneic Proteins Paracrine Signaling (Exo-d-MAPPS)”, a biological product in which the activity is based on AF-MSC-derived Exos capable to deliver immunomodulatory molecules and growth factors to the target cells. Herewith, we analyzed immunosuppressive capacity of Exo-d-MAPPS against human peripheral blood mononuclear cells (pbMNCs) and demonstrated that Exo-d-MAPPS efficiently suppressed generation of inflammatory phenotype in activated pbMNCs. Exo-d-MAPPS attenuated production of inflammatory cytokines and promoted generation of immunosuppressive phenotype in Lipopolysaccharide-primed pbMNCs. Exo-d-MAPPS treatment reduced expansion of inflammatory Th1 and Th17 cells and promoted generation of immunosuppressive T regulatory cells in the population of Concanavalin A-primed pbMNCs. Similarly, Exod-MAPPS treatment suppressed pro-inflammatory and promoted anti-inflammatory properties of α-GalCer-primed pbMNCs. In summing up, due to its capacity for suppression of activated pbMNCs, Exo-d-MAPPS should be further explored in animal models of acute and chronic inflammatory diseases as a poten-tially new remedy for the attenuation of detrimental immune response.

scholarly journals Extracellular vesicles produced by immunomodulatory cells harboring OX40 ligand and 4-1BB ligand enhance antitumor immunity

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Isadora Ferraz Semionatto ◽  
Soledad Palameta ◽  
Jéssica Marcelino Toscaro ◽  
Andrea Johanna Manrique-Rincón ◽  
Luciana Pereira Ruas ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Extracellular Vesicles ◽  
Immune Cells ◽  
Antitumor Immunity ◽  
Genetically Modified ◽  
Therapeutic Benefit ◽  
Target Cells ◽  
Tumor Vaccines ◽  
Therapeutic Vaccines ◽  
Ox40 Ligand

Abstract Genetically modified tumor cells harboring immunomodulators may be used as therapeutic vaccines to stimulate antitumor immunity. The therapeutic benefit of these tumor vaccines is extensively investigated and mechanisms by which they boost antitumor response may be further explored. Tumor cells are large secretors of extracellular vesicles (EVs). These EVs are able to vehiculate RNA and proteins to target cells, and engineered EVs also vehiculate recombinant proteins. In this study, we explore immunomodulatory properties of EVs derived from antitumor vaccines expressing the TNFSF ligands 4-1BBL and OX40L, modulating immune response mediated by immune cells and eliminating tumors. Our results suggest that the EVs secreted by genetically modified tumor cells harboring TNFSF ligands can induce T cell proliferation, inhibit the transcription factor FoxP3, associated with the maintenance of Treg phenotype, and enhance antitumor activity mediated by immune cells. The immunomodulatory extracellular vesicles have potential to be further engineered for developing new approaches for cancer therapy.

scholarly journals Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1763
Author(s):  
Elisabetta Chiaradia ◽  
Brunella Tancini ◽  
Carla Emiliani ◽  
Federica Delo ◽  
Roberto Maria Pellegrino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Extracellular Vesicles ◽  
Molecular Mechanisms ◽  
Cell Communication ◽  
Redox Status ◽  
Biological Properties ◽  
Stress Conditions ◽  
Target Cells ◽  
Redox Biology ◽  
Starting Point

Under physio-pathological conditions, cells release membrane-surrounded structures named Extracellular Vesicles (EVs), which convey their molecular cargo to neighboring or distant cells influencing their metabolism. Besides their involvement in the intercellular communication, EVs might represent a tool used by cells to eliminate unnecessary/toxic material. Here, we revised the literature exploring the link between EVs and redox biology. The first proof of this link derives from evidence demonstrating that EVs from healthy cells protect target cells from oxidative insults through the transfer of antioxidants. Oxidative stress conditions influence the release and the molecular cargo of EVs that, in turn, modulate the redox status of target cells. Oxidative stress-related EVs exert both beneficial or harmful effects, as they can carry antioxidants or ROS-generating enzymes and oxidized molecules. As mediators of cell-to-cell communication, EVs are also implicated in the pathophysiology of oxidative stress-related diseases. The review found evidence that numerous studies speculated on the role of EVs in redox signaling and oxidative stress-related pathologies, but few of them unraveled molecular mechanisms behind this complex link. Thus, the purpose of this review is to report and discuss this evidence, highlighting that the analysis of the molecular content of oxidative stress-released EVs (reminiscent of the redox status of originating cells), is a starting point for the use of EVs as diagnostic and therapeutic tools in oxidative stress-related diseases.

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