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Natural and Artificial Vesicles and Nanoparticles against Brain Diseases
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Natural and Artificial Vesicles and Nanoparticles against Brain Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 17930

Special Issue Editor

Dr. Pasquale Picone

E-Mail Website
Guest Editor
1. Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, 90128 Palermo, Italy
2. Istituto per la Ricerca e l’Innovazione Biomedica (IRIB), CNR, Via U. La Malfa 153, 90146 Palermo, Italy
Interests: neurodegeneration; mitochondrial dysfunction and oxidative stress; mitochondrial transplantation; nanotechnology and brain drug delivery systems; vesicles; immunotolerance and immunomodulation in multiple sclerosis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain diseases (BD) affect millions of people around the world. These pathologies (inflammatory, trauma, tumors, stroke and neurodegenerative disease) represent a considerable global social and economic burden and constitute an unquestionable emergency, and a grand challenge for neuroscientists. The presence of various physiological barriers limits accessibility to the brain and reduces the effectiveness of various therapies. Furthermore, the improvement of the solubility, stability and release of the drugs/molecules in specific brain regions and in particular target cells are essential factors in developing an effective therapy. Several studies have reported that extracellular vesicles (EVs) are released from cells of the central nervous system (CNS), playing a significant role in its functions. Indeed, EVs are involved in the control of neurogenesis, in the regulation of the biogenesis of myelin sheaths and in the repair of damaged neurons. For these effects, VEs can be used for therapeutic purposes or as brain drug delivery systems (BDDS). Furthermore, recently artificial nanovesicles, such as cell membrane-based systems, and nanoparticles (NP) have received increasing interest as BDDS to counter BD. EVs, artificial nanovesicles and NP can target a CNS cell-type in specific regions of the brain. In conclusion, EVs, artificial nanovesicles and NP, thanks to their capacities, may represent a promising strategy against BD. Therefore, authors are invited to present original research articles, review papers or communications focused on the EVs and artificial nanovesicles as therapeutic tools to contrast BD.

Dr. Pasquale Picone
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • brain diseases
  • extracellular vesicles
  • artificial nanovesicles
  • brain drug delivery systems
  • cell target
  • nanoparticles (NP)

Published Papers (6 papers)

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Editorial

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3 pages, 187 KiB  
Editorial
Nanobiotechnology: A New Frontier for Brain Disorders
by Pasquale Picone
Int. J. Mol. Sci. 2022, 23(17), 9603; https://doi.org/10.3390/ijms23179603 - 24 Aug 2022
Cited by 1 | Viewed by 964
Abstract
Brain disorders, such as neurodegenerative diseases (NDs) and tumors (more than 600 pathologies), are a serious health problem, resulting in brain dysfunctions that limit normal activities, with a significant economic impact [...] Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)

Research

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21 pages, 9410 KiB  
Article
The Mechanisms Underlying the Protective Action of Selenium Nanoparticles against Ischemia/Reoxygenation Are Mediated by the Activation of the Ca2+ Signaling System of Astrocytes and Reactive Astrogliosis
by Elena G. Varlamova, Egor A. Turovsky, Valentina A. Babenko and Egor Y. Plotnikov
Int. J. Mol. Sci. 2021, 22(23), 12825; https://doi.org/10.3390/ijms222312825 - 26 Nov 2021
Cited by 20 | Viewed by 1999
Abstract
In recent years, much attention has been paid to the study of the therapeutic effect of the microelement selenium, its compounds, especially selenium nanoparticles, with a large number of works devoted to their anticancer effects. Studies proving the neuroprotective properties of selenium nanoparticles [...] Read more.
In recent years, much attention has been paid to the study of the therapeutic effect of the microelement selenium, its compounds, especially selenium nanoparticles, with a large number of works devoted to their anticancer effects. Studies proving the neuroprotective properties of selenium nanoparticles in various neurodegenerative diseases began to appear only in the last 5 years. Nevertheless, the mechanisms of the neuroprotective action of selenium nanoparticles under conditions of ischemia and reoxygenation remain unexplored, especially for intracellular Ca2+ signaling and neuroglial interactions. This work is devoted to the study of the cytoprotective mechanisms of selenium nanoparticles in the neuroglial networks of the cerebral cortex under conditions of ischemia/reoxygenation. It was shown for the first time that selenium nanoparticles dose-dependently induce the generation of Ca2+ signals selectively in astrocytes obtained from different parts of the brain. The generation of these Ca2+ signals by astrocytes occurs through the release of Ca2+ ions from the endoplasmic reticulum through the IP3 receptor upon activation of the phosphoinositide signaling pathway. An increase in the concentration of cytosolic Ca2+ in astrocytes leads to the opening of connexin Cx43 hemichannels and the release of ATP and lactate into the extracellular medium, which trigger paracrine activation of the astrocytic network through purinergic receptors. Incubation of cerebral cortex cells with selenium nanoparticles suppresses ischemia-induced increase in cytosolic Ca2+ and necrotic cell death. Activation of A2 reactive astrocytes exclusively after ischemia/reoxygenation, a decrease in the expression level of a number of proapoptotic and proinflammatory genes, an increase in lactate release by astrocytes, and suppression of the hyperexcitation of neuronal networks formed the basis of the cytoprotective effect of selenium nanoparticles in our studies. Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)
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15 pages, 3831 KiB  
Article
Extracellular Vesicles from Human Teeth Stem Cells Trigger ATP Release and Promote Migration of Human Microglia through P2X4 Receptor/MFG-E8-Dependent Mechanisms
by Ugnė Jonavičė, Diana Romenskaja, Karolina Kriaučiūnaitė, Akvilė Jarmalavičiūtė, Justina Pajarskienė, Vytautas Kašėta, Virginijus Tunaitis, Tarja Malm, Rashid Giniatullin and Augustas Pivoriūnas
Int. J. Mol. Sci. 2021, 22(20), 10970; https://doi.org/10.3390/ijms222010970 - 11 Oct 2021
Cited by 5 | Viewed by 2249
Abstract
Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate the neuroinflammatory response of microglia remains largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human [...] Read more.
Extracellular vesicles (EVs) effectively suppress neuroinflammation and induce neuroprotective effects in different disease models. However, the mechanisms by which EVs regulate the neuroinflammatory response of microglia remains largely unexplored. Here, we addressed this issue by testing the action of EVs derived from human exfoliated deciduous teeth stem cells (SHEDs) on immortalized human microglial cells. We found that EVs induced a rapid increase in intracellular Ca2+ and promoted significant ATP release in microglial cells after 20 min of treatment. Boyden chamber assays revealed that EVs promoted microglial migration by 20%. Pharmacological inhibition of different subtypes of purinergic receptors demonstrated that EVs activated microglial migration preferentially through the P2X4 receptor (P2X4R) pathway. Proximity ligation and co-immunoprecipitation assays revealed that EVs promote association between milk fat globule-epidermal growth factor-factor VIII (MFG-E8) and P2X4R proteins. Furthermore, pharmacological inhibition of αVβ3/αVβ5 integrin suppressed EV-induced cell migration and formation of lipid rafts in microglia. These results demonstrate that EVs promote microglial motility through P2X4R/MFG-E8-dependent mechanisms. Our findings provide novel insights into the molecular mechanisms through which EVs target human microglia that may be exploited for the development of new therapeutic strategies targeting disease-associated neuroinflammation. Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)
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18 pages, 3001 KiB  
Article
Tomato Bushy Stunt Virus Nanoparticles as a Platform for Drug Delivery to Shh-Dependent Medulloblastoma
by Chiara Lico, Barbara Tanno, Luca Marchetti, Flavia Novelli, Paola Giardullo, Caterina Arcangeli, Simonetta Pazzaglia, Maurizio S. Podda, Luca Santi, Roberta Bernini, Selene Baschieri and Mariateresa Mancuso
Int. J. Mol. Sci. 2021, 22(19), 10523; https://doi.org/10.3390/ijms221910523 - 29 Sep 2021
Cited by 9 | Viewed by 2650
Abstract
Medulloblastoma (MB) is a primary central nervous system tumor affecting mainly young children. New strategies of drug delivery are urgent to treat MB and, in particular, the SHH-dependent subtype—the most common in infants—in whom radiotherapy is precluded due to the severe neurological side [...] Read more.
Medulloblastoma (MB) is a primary central nervous system tumor affecting mainly young children. New strategies of drug delivery are urgent to treat MB and, in particular, the SHH-dependent subtype—the most common in infants—in whom radiotherapy is precluded due to the severe neurological side effects. Plant virus nanoparticles (NPs) represent an innovative solution for this challenge. Tomato bushy stunt virus (TBSV) was functionally characterized as a carrier for drug targeted delivery to a murine model of Shh-MB. The TBSV NPs surface was genetically engineered with peptides for brain cancer cell targeting, and the modified particles were produced on a large scale using Nicotiana benthamiana plants. Tests on primary cultures of Shh-MB cells allowed us to define the most efficient peptides able to induce specific uptake of TBSV. Immunofluorescence and molecular dynamics simulations supported the hypothesis that the specific targeting of the NPs was mediated by the interaction of the peptides with their natural partners and reinforced by the presentation in association with the virus. In vitro experiments demonstrated that the delivery of Doxorubicin through the chimeric TBSV allowed reducing the dose of the chemotherapeutic agent necessary to induce a significant decrease in tumor cells viability. Moreover, the systemic administration of TBSV NPs in MB symptomatic mice, independently of sex, confirmed the ability of the virus to reach the tumor in a specific manner. A significant advantage in the recognition of the target appeared when TBSV NPs were functionalized with the CooP peptide. Overall, these results open new perspectives for the use of TBSV as a vehicle for the targeted delivery of chemotherapeutics to MB in order to reduce early and late toxicity. Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)
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Review

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20 pages, 2999 KiB  
Review
Exosomes in Alzheimer’s Disease: From Being Pathological Players to Potential Diagnostics and Therapeutics
by Hagar M. Soliman, Ghada A. Ghonaim, Shaza M. Gharib, Hitesh Chopra, Aya K. Farag, Mohamed H. Hassanin, Abdalrazeq Nagah, Mahmoud Emad-Eldin, Nevertary E. Hashem, Galal Yahya, Sherif E. Emam, Abdalla E. A. Hassan and Mohamed S. Attia
Int. J. Mol. Sci. 2021, 22(19), 10794; https://doi.org/10.3390/ijms221910794 - 06 Oct 2021
Cited by 32 | Viewed by 5783
Abstract
Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson’s and Alzheimer’s disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers [...] Read more.
Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson’s and Alzheimer’s disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions. Recently, EXOs provided potential drug delivery opportunities in AD and promising future clinical applications with the diagnosis of NDD and were studied for their usefulness in disease detection and prediction prior to the emergence of symptoms. In the future, the microfluidics technique will play an essential role in isolating and detecting EXOs to diagnose AD before the development of advanced symptoms. This review is not reiterative literature but will discuss why EXOs have strong potential in treating AD and how they can be used as a tool to predict and diagnose this disorder. Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)
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12 pages, 1739 KiB  
Review
Multiple Sclerosis: Focus on Extracellular and Artificial Vesicles, Nanoparticles as Potential Therapeutic Approaches
by Domenico Nuzzo and Pasquale Picone
Int. J. Mol. Sci. 2021, 22(16), 8866; https://doi.org/10.3390/ijms22168866 - 18 Aug 2021
Cited by 13 | Viewed by 3153
Abstract
Multiple sclerosis (MS) is an autoimmune disease of the Central Nervous System, characterized by an inflammatory process leading to the destruction of myelin with neuronal death and neurodegeneration. In MS, lymphocytes cross the blood-brain barrier, creating inflammatory demyelinated plaques located primarily in the [...] Read more.
Multiple sclerosis (MS) is an autoimmune disease of the Central Nervous System, characterized by an inflammatory process leading to the destruction of myelin with neuronal death and neurodegeneration. In MS, lymphocytes cross the blood-brain barrier, creating inflammatory demyelinated plaques located primarily in the white matter. MS potential treatments involve various mechanisms of action on immune cells, immunosuppression, inhibition of the passage through the blood-brain barrier, and immunotolerance. Bio-nanotechnology represents a promising approach to improve the treatment of autoimmune diseases by its ability to affect the immune responses. The use of nanotechnology has been actively investigated for the development of new MS therapies. In this review, we summarize the results of the studies on natural and artificial vesicles and nanoparticles, and take a look to the future clinical perspectives for their application in the MS therapy. Full article
(This article belongs to the Special Issue Natural and Artificial Vesicles and Nanoparticles against Brain Diseases)
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