Current Perspectives on Delivery Systems Using Extracellular Vesicles in Neurological Disease

2020 ◽  
Vol 26 (7) ◽  
pp. 764-771
Author(s):  
Phuong H.L. Tran ◽  
Wei Duan ◽  
Beom-Jin Lee ◽  
Thao T.D. Tran
Keyword(s):  
Surface Modification ◽  
Extracellular Vesicles ◽  
Neurological Disease ◽  
Delivery Systems ◽  
Clinical Applications ◽  
Target Cells ◽  
Therapeutic Factors ◽  
The Past ◽  
Different Types ◽  
Therapeutic Molecules

: Extracellular vesicles have an excellent ability to transfer their contents to cells. Extracellular vesicles can also be engineered to deliver therapeutic molecules to target cells. Although a number of studies have exploited synthesized nanoparticles in the treatment of neurological disease in the past few years, extracellular vesicles have been investigated and shown tremendous promise for clinical applications because they are safe and have strong targeting specificity. Different types of extracellular vesicles have been studied and modified for delivering therapeutic factors in neurological disease, including extracellular vesicles loaded with natural therapeutic factors and therapeutic molecules. In this review, we discuss delivery systems using extracellular vesicles containing molecules of interest and then focus on main strategies used for EV loading and surface modification. Discussing these important issues will support and facilitate the design and development of promising techniques and products for neurological therapy.

scholarly journals On the Choice of the Extracellular Vesicles for Therapeutic Purposes

2019 ◽  
Vol 20 (2) ◽  
pp. 236 ◽  
Author(s):  
Claudia Campanella ◽  
Celeste Caruso Bavisotto ◽  
Mariantonia Logozzi ◽  
Antonella Marino Gammazza ◽  
Davide Mizzoni ◽  
...  
Keyword(s):  
Regenerative Medicine ◽  
Extracellular Vesicles ◽  
Lipid Membrane ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Free Form ◽  
Target Cells ◽  
Disease Biomarkers ◽  
Cellular Source ◽  
Therapeutic Molecules

Extracellular vesicles (EVs) are lipid membrane vesicles released by all human cells and are widely recognized to be involved in many cellular processes, both in physiological and pathological conditions. They are mediators of cell-cell communication, at both paracrine and systemic levels, and therefore they are active players in cell differentiation, tissue homeostasis, and organ remodeling. Due to their ability to serve as a cargo for proteins, lipids, and nucleic acids, which often reflects the cellular source, they should be considered the future of the natural nanodelivery of bio-compounds. To date, natural nanovesicles, such as exosomes, have been shown to represent a source of disease biomarkers and have high potential benefits in regenerative medicine. Indeed, they deliver both chemical and bio-molecules in a way that within exosomes drugs are more effective that in their exosome-free form. Thus, to date, we know that exosomes are shuttle disease biomarkers and probably the most effective way to deliver therapeutic molecules within target cells. However, we do not know exactly which exosomes may be used in therapy in avoiding side effects as well. In regenerative medicine, it will be ideal to use autologous exosomes, but it seems not ideal to use plasma-derived exosomes, as they may contain potentially dangerous molecules. Here, we want to present and discuss a contradictory relatively unmet issue that is the lack of a general agreement on the choice for the source of extracellular vesicles for therapeutic use.

scholarly journals Active Targeting Strategies Using Biological Ligands for Nanoparticle Drug Delivery Systems

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 640 ◽  
Author(s):  
Jihye Yoo ◽  
Changhee Park ◽  
Gawon Yi ◽  
Donghyun Lee ◽  
Heebeom Koo
Keyword(s):  
Drug Delivery ◽  
Surface Modification ◽  
Small Molecules ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Active Targeting ◽  
Target Cells ◽  
Specific Receptors ◽  
Nanoparticle Drug Delivery

Targeting nanoparticle (NP) carriers to sites of disease is critical for their successful use as drug delivery systems. Along with optimization of physicochemical properties, researchers have focused on surface modification of NPs with biological ligands. Such ligands can bind specific receptors on the surface of target cells. Furthermore, biological ligands can facilitate uptake of modified NPs, which is referred to as ‘active targeting’ of NPs. In this review, we discuss recent applications of biological ligands including proteins, polysaccharides, aptamers, peptides, and small molecules for NP-mediated drug delivery. We prioritized studies that have demonstrated targeting in animals over in vitro studies. We expect that this review will assist biomedical researchers working with NPs for drug delivery and imaging.

scholarly journals miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 347 ◽  
Author(s):  
Enrico Ragni ◽  
Carlotta Perucca Orfei ◽  
Antonietta Rosa Silini ◽  
Alessandra Colombini ◽  
Marco Viganò ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mesenchymal Stromal Cells ◽  
Amniotic Membrane ◽  
Stromal Cells ◽  
Reference Genes ◽  
Target Cells ◽  
Human Amniotic Membrane ◽  
U6 Snrna ◽  
Therapeutic Molecules ◽  
The Impact

Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields.

scholarly journals Extracellular Vesicles as Biomarkers and Therapeutic Tools: From Pre-Clinical to Clinical Applications

Biology ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 359
Author(s):  
Maria Chiara Ciferri ◽  
Rodolfo Quarto ◽  
Roberta Tasso
Keyword(s):  
Clinical Trials ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Cell Types ◽  
Storage Conditions ◽  
Clinical Applications ◽  
The Other ◽  
The Past ◽  
Therapeutic Tools ◽  
And Storage

Extracellular vesicles (EVs) are ubiquitous masters of intercellular communication, being detectable in tissues, circulation, and body fluids. Their complex cargo reflects the (patho)physiologic status of the cells from which they originate. Due to these properties, the potential of EVs, and in particular exosomes, to serve as biomarkers or therapeutics has grown exponentially over the past decade. On one side, numerous studies have demonstrated that EV-associated nucleic acids and proteins are implicated in cancer progression, as well as neurodegenerative, infectious, and autoimmune disorders. On the other, the therapeutic use of EVs secreted by various cell types, and in particular stem/progenitor cells, present significant advantages in comparison to the corresponding parental cells, such as the less complex production and storage conditions. In this review, we examine some of the major pre-clinical studies dealing with EVs and exosomes, that led to the development of numerous completed clinical trials.

scholarly journals Characterization of RNA in Extracellular Vesicles

2021 ◽  
Vol 11 (16) ◽  
pp. 7520
Author(s):  
Silvia Fischer ◽  
Elisabeth Deindl
Keyword(s):  
Extracellular Vesicles ◽  
Noncoding Rnas ◽  
Circular Rnas ◽  
Target Cells ◽  
Multivesicular Bodies ◽  
Bioactive Lipids ◽  
Rna Molecules ◽  
Different Types ◽  
Endosomal Pathway

Extracellular vesicles (EVs) are important players in the communication between different kinds of cells by delivering their content, consisting of different types of RNA, proteins, bioactive lipids, or signaling nucleotides, into their target cells. Several types of EVs are distinguished: (1) exosomes with sizes from 30 to 150 nm originate from the endosomal pathway and form intracellular multivesicular bodies (MVBs), which fuse to the plasma membrane before their secretion. (2) EVs with sizes ranging from 100 to 1000 nm in diameter are formed during cell surface budding. (3) Apoptotic bodies with diameters from 500 to 2000 nm are released from blebbing of the cell membrane of apoptotic cells. It is well established that various RNA molecules such as coding RNAs and noncoding RNAs (long noncoding RNAs, microRNAs, circular RNAs, and rRNAs) are present in different amounts in EVs depending on the type and origin of EV. Here we will give an overview of methods to isolate different types of EVs and to quantify and characterize different RNA species.

Ultrasound-triggered immunotherapy for cancer treatment: An update

2021 ◽  
Vol 22 ◽  
Author(s):  
Debasmita Mukhopadhyay ◽  
Amal Ahmed ◽  
Catherine Sano ◽  
Nahid Awad ◽  
Nour AlSawaftah ◽  
...  
Keyword(s):  
Immune Cell ◽  
Cell Membrane Permeability ◽  
Target Cells ◽  
Cancer Therapies ◽  
Antibody Dependent Cellular Cytotoxicity ◽  
Cell Growth Inhibition ◽  
Cancer Treatments ◽  
The Past ◽  
Promising Therapeutic Approach ◽  
Therapeutic Molecules

: Over the past few decades, immunotherapy has emerged as a promising therapeutic approach to treat some types of cancer. Moreover, antibody-based cancer therapies can trigger apoptosis and cell growth inhibition to induce immune cell destruction of target cells through antibody-dependent cellular cytotoxicity (ADCC). Nevertheless, immunotherapeutic efficiency is often restricted to either deficient delivery or low accumulation of therapeutic molecules at the tumor site. Therefore, exposing immunoliposomes to ultrasound can effectively improve drug accessibility by enhancing cell membrane permeability and drug release. This review summarizes existing traditional cancer treatments and their limitations, emphasizing the recent advancements in ultrasound-triggered immunotherapy.

scholarly journals Extracellular Vesicles: A Therapeutic Option for Liver Fibrosis

2020 ◽  
Vol 21 (12) ◽  
pp. 4255
Author(s):  
Stefania Bruno ◽  
Giulia Chiabotto ◽  
Giovanni Camussi
Keyword(s):  
Liver Fibrosis ◽  
Extracellular Vesicles ◽  
Therapeutic Option ◽  
Membrane Vesicles ◽  
Hepatocyte Proliferation ◽  
Target Cells ◽  
In Vivo Models ◽  
Pathological Conditions ◽  
Different Types

Extracellular vesicles (EVs) are a heterogeneous population of small membrane vesicles released by all types of cells in both physiological and pathological conditions. EVs shuttle different types of molecules and are able to modify the behavior of target cells by various mechanisms of action. In this review, we have summarized the papers present in the literature, to our acknowledge, that reported the EV effects on liver diseases. EVs purified from serum, stem cells, and hepatocytes were investigated in different experimental in vivo models of liver injury and in particular of liver fibrosis. Despite the different EV origin and the different types of injury (toxic, ischemic, diet induced, and so on), EVs showed an anti-fibrotic effect. In particular, EVs had the capacities to inhibit activation of hepatic stellate cells, one of the major players of liver fibrosis development; to reduce inflammation and apoptosis; to counteract the oxidative stress; and to increase hepatocyte proliferation, contributing to reducing fibrosis and ameliorating liver function and morphology.

scholarly journals Hydrogels: 3D Drug Delivery Systems for Nanoparticles and Extracellular Vesicles

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1694
Author(s):  
Yashna Chabria ◽  
Garry Duffy ◽  
Aoife Lowery ◽  
Róisín Dwyer
Keyword(s):  
Extracellular Vesicles ◽  
Targeted Delivery ◽  
Prolonged Exposure ◽  
Delivery Systems ◽  
The Body ◽  
Target Site ◽  
Target Cells ◽  
Clinical Settings ◽  
Sustained Delivery ◽  
Stimuli Sensitive

Synthetic and naturally occurring nano-sized particles present versatile vehicles for the delivery of therapy in a range of clinical settings. Their small size and modifiable physicochemical properties support refinement of targeting capabilities, immune response, and therapeutic cargo, but rapid clearance from the body and limited efficacy remain a major challenge. This highlights the need for a local sustained delivery system for nanoparticles (NPs) and extracellular vesicles (EVs) at the target site that will ensure prolonged exposure, maximum efficacy and dose, and minimal toxicity. Biocompatible hydrogels loaded with therapeutic NPs/EVs hold immense promise as cell-free sustained and targeted delivery systems in a range of disease settings. These bioscaffolds ensure retention of the nano-sized particles at the target site and can also act as controlled release systems for therapeutics over a prolonged period of time. The encapsulation of stimuli sensitive components into hydrogels supports the release of the content on-demand. In this review, we highlight the prospect of the sustained and prolonged delivery of these nano-sized therapeutic entities from hydrogels for broad applications spanning tissue regeneration and cancer treatment. Further understanding of the parameters controlling the release rate of these particles and efficient transfer of cargo to target cells will be fundamental to success.

scholarly journals Micro RNAs are minor constituents of extracellular vesicles and are hardly delivered to target cells

2020 ◽  
Author(s):  
Manuel Albanese ◽  
Yen-Fu Adam Chen ◽  
Corinna Hüls ◽  
Kathrin Gärtner ◽  
Takanobu Tagawa ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Mammalian Cells ◽  
Cell Communication ◽  
Cell Types ◽  
Convincing Evidence ◽  
Target Cells ◽  
Mrna Targets ◽  
Negative Results ◽  
Micro Rnas ◽  
Different Types

ABSTRACTMammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells’ transcriptome. The extent to which miRNAs are exported via the EV route and whether they contribute to cell-cell communication are controversial. To address these issues, we analyzed the capacity of EVs to deliver packaged miRNAs into target cells and to exert biological functions. We applied well-defined approaches to produce and characterize purified EVs with or without specific viral miRNAs. We found that only a small fraction of EVs carried miRNAs. EVs readily bound to different target cell types, but there was no EV-cell membrane fusion or delivery of cargo. Importantly, the functionality of cells exposed to miRNA-carrying EVs was not affected. These results suggest EV-borne miRNAs do not act as effectors and question their relevancy in paracrine cell-to-cell communication.AUTHOR SUMMARYThe majority of metazoan cells release vesicles of different types and origins, such as exosomes and microvesicles, now collectively termed extracellular vesicles (EVs). EVs have gained much attention because they contain microRNAs (miRNAs) and thus could regulate their specific mRNA targets in recipient or acceptor cells that take up EVs. Using a novel fusion assay with superior sensitivity and specificity, we revisited this claim but found no convincing evidence for an efficient functional uptake of EVs in many different cell lines and primary human blood cells. Even EVs engineered to fuse and deliver their miRNA cargo to recipient cells had no measurable effect on target mRNAs in very carefully controlled, quantitative experiments. Our negative results clearly indicate that EVs do not act as vehicles for miRNA-based cell-to-cell communication.

scholarly journals MicroRNAs are minor constituents of extracellular vesicles that are rarely delivered to target cells

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009951
Author(s):  
Manuel Albanese ◽  
Yen-Fu Adam Chen ◽  
Corinna Hüls ◽  
Kathrin Gärtner ◽  
Takanobu Tagawa ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Target Cell ◽  
Mammalian Cells ◽  
Cell Communication ◽  
Cell Types ◽  
Target Cells ◽  
Messenger Rnas ◽  
Biological Functions ◽  
Different Types ◽  
The Stability

Mammalian cells release different types of vesicles, collectively termed extracellular vesicles (EVs). EVs contain cellular microRNAs (miRNAs) with an apparent potential to deliver their miRNA cargo to recipient cells to affect the stability of individual mRNAs and the cells’ transcriptome. The extent to which miRNAs are exported via the EV route and whether they contribute to cell-cell communication are controversial. To address these issues, we defined multiple properties of EVs and analyzed their capacity to deliver packaged miRNAs into target cells to exert biological functions. We applied well-defined approaches to produce and characterize purified EVs with or without specific viral miRNAs. We found that only a small fraction of EVs carried miRNAs. EVs readily bound to different target cell types, but EVs did not fuse detectably with cellular membranes to deliver their cargo. We engineered EVs to be fusogenic and document their capacity to deliver functional messenger RNAs. Engineered fusogenic EVs, however, did not detectably alter the functionality of cells exposed to miRNA-carrying EVs. These results suggest that EV-borne miRNAs do not act as effectors of cell-to-cell communication.

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