scholarly journals Extracellular Vesicles as an Efficient and Versatile System for Drug Delivery

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2191 ◽  
Author(s):  
Xuan T. T. Dang ◽  
Jayasinghe Migara Kavishka ◽  
Daniel Xin Zhang ◽  
Marco Pirisinu ◽  
Minh T. N. Le

Despite the recent advances in drug development, the majority of novel therapeutics have not been successfully translated into clinical applications. One of the major factors hindering their clinical translation is the lack of a safe, non-immunogenic delivery system with high target specificity upon systemic administration. In this respect, extracellular vesicles (EVs), as natural carriers of bioactive cargo, have emerged as a promising solution and can be further modified to improve their therapeutic efficacy. In this review, we provide an overview of the biogenesis pathways, biochemical features, and isolation methods of EVs with an emphasis on their many intrinsic properties that make them desirable as drug carriers. We then describe in detail the current advances in EV therapeutics, focusing on how EVs can be engineered to achieve improved target specificity, better circulation kinetics, and efficient encapsulation of therapeutic payloads. We also identify the challenges and obstacles ahead for clinical translation and provide an outlook on the future perspective of EV-based therapeutics.

2021 ◽  
Author(s):  
Shaobing Zhou ◽  
Rui Su ◽  
Xiang Xiong ◽  
Yingping Li ◽  
Xiaoqing Wei ◽  
...  

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...


Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4604
Author(s):  
Taketo Kato ◽  
Jody V. Vykoukal ◽  
Johannes F. Fahrmann ◽  
Samir Hanash

Extracellular vesicles (EVs) are nano-sized lipid-bound particles containing proteins, nucleic acids and metabolites released by cells. They have been identified in body fluids including blood, saliva, sputum and pleural effusions. In tumors, EVs derived from cancer and immune cells mediate intercellular communication and exchange, and can affect immunomodulatory functions. In the context of lung cancer, emerging evidence implicates EV involvement during various stages of tumor development and progression, including angiogenesis, epithelial to mesenchymal transformation, immune system suppression, metastasis and drug resistance. Additionally, tumor-derived EVs (TDEs) have potential as a liquid biopsy source and as a means of therapeutic targeting, and there is considerable interest in developing clinical applications for EVs in these contexts. In this review, we consider the biogenesis, components, biological functions and isolation methods of EVs, and the implications for their clinical utility for diagnostic and therapeutic applications in lung cancer.


Author(s):  
Florian A. Huber ◽  
Roman Guggenberger

AbstractRecent investigations have focused on the clinical application of artificial intelligence (AI) for tasks specifically addressing the musculoskeletal imaging routine. Several AI applications have been dedicated to optimizing the radiology value chain in spine imaging, independent from modality or specific application. This review aims to summarize the status quo and future perspective regarding utilization of AI for spine imaging. First, the basics of AI concepts are clarified. Second, the different tasks and use cases for AI applications in spine imaging are discussed and illustrated by examples. Finally, the authors of this review present their personal perception of AI in daily imaging and discuss future chances and challenges that come along with AI-based solutions.


2021 ◽  
Vol 12 ◽  
pp. 204173142110190
Author(s):  
Jung-Hwan Lee ◽  
Ji-Young Yoon ◽  
Jun Hee Lee ◽  
Hae-Hyoung Lee ◽  
Jonathan C Knowles ◽  
...  

Extracellular vesicles (EVs), including exosomes, carry the genetic packages of RNA, DNA, and proteins and are heavily involved in cell-cell communications and intracellular signalings. Therefore, EVs are spotlighted as therapeutic mediators for the treatment of injured and dysfunctional tissues as well as biomarkers for the detection of disease status and progress. Several key issues in EVs, including payload content and bioactivity, targeting and bio-imaging ability, and mass-production, need to be improved to enable effective therapeutics and clinical translation. For this, significant efforts have been made recently, including genetic modification, biomolecular and chemical treatment, application of physical/mechanical cues, and 3D cultures. Here we communicate those recent technological advances made mainly in the biogenesis process of EVs or at post-collection stages, which ultimately aimed to improve the therapeutic efficacy in tissue healing and disease curing and the possibility of clinical translation. This communication will help tissue engineers and biomaterial scientists design and produce EVs optimally for tissue regenerative therapeutics.


2021 ◽  
Vol 22 (24) ◽  
pp. 13513
Author(s):  
Min-Hyeok Kim ◽  
Danny van Noort ◽  
Jong Hwan Sung ◽  
Sungsu Park

Extracellular vesicles (EVs) are a group of membrane vesicles that play important roles in cell-to-cell and interspecies/interkingdom communications by modulating the pathophysiological conditions of recipient cells. Recent evidence has implied their potential roles in the gut–brain axis (GBA), which is a complex bidirectional communication system between the gut environment and brain pathophysiology. Despite the evidence, the roles of EVs in the gut microenvironment in the GBA are less highlighted. Moreover, there are critical challenges in the current GBA models and analyzing techniques for EVs, which may hinder the research. Currently, advances in organ-on-a-chip (OOC) technologies have provided a promising solution. Here, we review the potential effects of EVs occurring in the gut environment on brain physiology and behavior and discuss how to apply OOCs to research the GBA mediated by EVs in the gut microenvironment.


2020 ◽  
Author(s):  
Ayako Kurimoto ◽  
Yuki Kawasaki ◽  
Toshiki Ueda ◽  
Tatsutoshi Inuzuka

AbstractExtracellular vesicles (EVs) have gained attention as potential targets of early diagnostics and prognosis in the field of liquid biopsy. Despite clinical potentials, the best method to isolate EVs from specimens remains controversial due to low purity, low specificity, and lack of reproducibility with current isolation methods. Here we show that a chelating reagent enhances the recovery efficiency of EVs from crude biological samples by immunoprecipitation using an anti-CD9 antibody. Proteomic and western blotting analyses show that the EVs isolated using the chelating reagent contain a wider variety of proteins than those isolated with PBS.


Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4844
Author(s):  
Mareike Waldenmaier ◽  
Tanja Seibold ◽  
Thomas Seufferlein ◽  
Tim Eiseler

Even with all recent advances in cancer therapy, pancreatic cancer still has a dismal 5-year survival rate of less than 7%. The most prevalent tumor subtype is pancreatic ductal adenocarcinoma (PDAC). PDACs display an extensive crosstalk with their tumor microenvironment (TME), e.g., pancreatic stellate cells, but also immune cells to regulate tumor growth, immune evasion, and metastasis. In addition to crosstalk in the local TME, PDACs were shown to induce the formation of pre-metastatic niches in different organs. Recent advances have attributed many of these interactions to intercellular communication by small extracellular vesicles (sEVs, exosomes). These nanovesicles are derived of endo-lysosomal structures (multivesicular bodies) with a size range of 30–150 nm. sEVs carry various bioactive cargos, such as proteins, lipids, DNA, mRNA, or miRNAs and act in an autocrine or paracrine fashion to educate recipient cells. In addition to tumor formation, progression, and metastasis, sEVs were described as potent biomarker platforms for diagnosis and prognosis of PDAC. Advances in sEV engineering have further indicated that sEVs might once be used as effective drug carriers. Thus, extensive sEV-based communication and applications as platform for biomarker analysis or vehicles for treatment suggest a major impact of sEVs in future PDAC research.


Viruses ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 486 ◽  
Author(s):  
Santosh Kumar ◽  
Kaining Zhi ◽  
Ahona Mukherji ◽  
Kelli Gerth

In January 2020, Chinese health agencies reported an outbreak of a novel coronavirus-2 (CoV-2) which can lead to severe acute respiratory syndrome (SARS). The virus, which belongs to the coronavirus family (SARS-CoV-2), was named coronavirus disease 2019 (COVID-19) and declared a pandemic by the World Health Organization (WHO). Full-length genome sequences of SARS-CoV-2 showed 79.6% sequence identity to SARS-CoV, with 96% identity to a bat coronavirus at the whole-genome level. COVID-19 has caused over 133,000 deaths and there are over 2 million total confirmed cases as of 15 April 2020. Current treatment plans are still under investigation due to a lack of understanding of COVID-19. One potential mechanism to slow disease progression is the use of antiviral drugs to either block the entry of the virus or interfere with viral replication and maturation. Currently, antiviral drugs, including chloroquine/hydroxychloroquine, remdesivir, and lopinavir/ritonavir, have shown effective inhibition of SARS-CoV-2 in vitro. Due to the high dose needed and narrow therapeutic window, many patients are experiencing severe side effects with the above drugs. Hence, repurposing these drugs with a proper formulation is needed to improve the safety and efficacy for COVID-19 treatment. Extracellular vesicles (EVs) are a family of natural carriers in the human body. They play a critical role in cell-to-cell communications. EVs can be used as unique drug carriers to deliver protease inhibitors to treat COVID-19. EVs may provide targeted delivery of protease inhibitors, with fewer systemic side effects. More importantly, EVs are eligible for major aseptic processing and can be upscaled for mass production. Currently, the FDA is facilitating applications to treat COVID-19, which provides a very good chance to use EVs to contribute in this combat.


2019 ◽  
Vol 127 (2) ◽  
pp. 645-653 ◽  
Author(s):  
Ivan J. Vechetti

Extracellular vesicles (EVs) were initially characterized as “garbage bags” with the purpose of removing unwanted material from cells. It is now becoming clear that EVs mediate intercellular communication between distant cells through a transfer of genetic material, a process important to the systemic adaptation in physiological and pathological conditions. Although speculative, it has been suggested that the majority of EVs that make it into the bloodstream would be coming from skeletal muscle, since it is one of the largest organs in the human body. Although it is well established that skeletal muscle secretes peptides (currently known as myokines) into the bloodstream, the notion that skeletal muscle releases EVs is in its infancy. Besides intercellular communication and systemic adaptation, EV release could represent the mechanism by which muscle adapts to certain stimuli. This review summarizes the current understanding of EV biology and biogenesis and current isolation methods and briefly discusses the possible role EVs have in regulating skeletal muscle mass.


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