Extracellular vesicles as a next-generation drug delivery platform

Nature Nanotechnology, Journal Year: 2021, Volume and Issue: 16(7), P. 748 - 759

Published: July 1, 2021

Language: Английский

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Extracellular vesicles as drug delivery systems: Why and how?

Advanced Drug Delivery Reviews, Journal Year: 2020, Volume and Issue: 159, P. 332 - 343

Published: Jan. 1, 2020

Over the past decades, a multitude of synthetic drug delivery systems has been developed and introduced to market. However, applications such are limited due inefficiency, cytotoxicity and/or immunogenicity. At same time, field natural carrier grown rapidly. One most prominent examples carriers extracellular vesicles (EVs). EVs cell-derived membranous particles which play important roles in intercellular communication. possess number characteristics that qualify them as promising vehicles for delivery. In order take advantage these attributes, an in-depth understanding why unique how we can exploit their qualities is pivotal. Here, review EV features relevant highlight emerging strategies make use those loading targeted

Language: Английский

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The Use of Alternative Strategies for Enhanced Nanoparticle Delivery to Solid Tumors

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(3), P. 1746 - 1803

Published: Jan. 14, 2021

Nanomaterial (NM) delivery to solid tumors has been the focus of intense research for over a decade. Classically, scientists have tried improve NM by employing passive or active targeting strategies, making use so-called enhanced permeability and retention (EPR) effect. This phenomenon is made possible due leaky tumor vasculature through which NMs can leave bloodstream, traverse gaps in endothelial lining vessels, enter tumor. Recent studies shown that despite many efforts employ EPR effect, this process remains very poor. Furthermore, role effect called into question, where it suggested

Language: Английский

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The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy

Acta Pharmaceutica Sinica B, Journal Year: 2020, Volume and Issue: 10(11), P. 2156 - 2170

Published: April 19, 2020

Macrophages have a leading position in the tumor microenvironment (TME) which paves way to carcinogenesis. Initially, monocytes and macrophages are recruited sites where develops. Under guidance of different microenvironmental signals, would polarize into two functional phenotypes, named as classically activated (M1) alternatively (M2). Contrary anti-tumor effect M1, M2 exerts anti-inflammatory tumorigenic characters. In progressive tumor, tumor-associated (TAMs) majority, being vital regulators reacting upon TME. This review elaborates on role TAMs progression. Furthermore, prospective macrophage-focused therapeutic strategies, including drugs not only clinical trials but also at primary research stages, summarized followed by discussion about their application values. Nanoparticulate systems with efficient drug delivery improved antitumor summed up this article.

Language: Английский

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Recent Advances in miRNA Delivery Systems

Methods and Protocols, Journal Year: 2021, Volume and Issue: 4(1), P. 10 - 10

Published: Jan. 20, 2021

MicroRNAs (miRNAs) represent a family of short non-coding regulatory RNA molecules that are produced in tissue and time-specific manner to orchestrate gene expression post-transcription. MiRNAs hybridize target mRNA(s) induce translation repression or mRNA degradation. Functional studies have demonstrated miRNAs engaged virtually every physiological process and, consequently, miRNA dysregulations been linked multiple human pathologies. Thus, mimics anti-miRNAs restore downregulate aberrantly expressed miRNAs, respectively, highly sought-after therapeutic strategies for effective manipulation levels. In this regard, carrier vehicles facilitate proficient safe delivery miRNA-based therapeutics fundamental the clinical success these pharmaceuticals. Here, we highlight strengths weaknesses current state-of-the-art viral non-viral systems provide perspective on how tools can be exploited improve outcomes therapeutics.

Language: Английский

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Recent progress in targeted delivery vectors based on biomimetic nanoparticles

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: June 7, 2021

Abstract Over the past decades, great interest has been given to biomimetic nanoparticles (BNPs) since rise of targeted drug delivery systems and nanotechnology. Biological vectors including cell membranes, extracellular vesicles (EVs), viruses are considered promising candidates for owing their biocompatibility biodegradability. BNPs, integration biological functional agents, anticipated load cargos or camouflage synthetic achieve delivery. Despite excellent intrinsic properties, natural deliberately modified endow multiple functions such as good permeability, improved loading capability, high specificity. Through structural modification transformation vectors, they pervasively utilized more effective vehicles that can deliver contrast chemotherapy drugs, nucleic acids, genes target sites refractory disease therapy. This review summarizes recent advances in based on EVs, viruses, highlighting potential applications BNPs fields biomedical imaging therapy industry, well discussing possibility clinical translation exploitation trend these BNPs.

Language: Английский

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Characterizing Extracellular Vesicles and Their Diverse RNA Contents

Frontiers in Genetics, Journal Year: 2020, Volume and Issue: 11

Published: July 17, 2020

Cells release nanometer-scale, lipid bilayer-enclosed biomolecular packages (extracellular vesicles; EVs) into their surrounding environment. EVs are hypothesized to be intercellular communication agents that regulate physiological states by transporting biomolecules between near and distant cells. The research community has consistently advocated for the importance of RNA contents in demonstrating that: 1) EV-related can detected a liquid biopsy, 2) disease significantly alter contents, 3) sensitive specific biopsies implemented precision medicine settings measuring EV-derived contents. Furthermore, have medical potential beyond diagnostics. Both natural engineered being investigated therapeutic applications such as regenerative drug delivery agents. This review focuses specifically on EV characterization, analysis content, functional implications. NIH extracellular (ERC) program catapulted human from an profiling standpoint standardizing pipeline working with transcriptomics data, creating centralized database scientific community. There currently thousands RNA-sequencing profiles hosted Extracellular Atlas alone \citep{Murillo2019}, encompassing variety biofluid types health conditions. While number significant discoveries been made through these studies individually, integrative analyses data thus far limited. A primary focus ERC over next five years is bring higher resolution tools so investigators isolate analyze sub-populations, ultimately single sourced discrete cell types, tissues, complex biofluids. Higher techniques will essential evaluating roles circulating at level which impacts clinical decision making. We expect advances microfluidic technologies drive near-term innovation about diverse EVs. Long-term translation EV-based mainstay diagnostic tool depend upon identifying robust patterns genetic material correlate change status.

Language: Английский

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Three-dimensional culture of MSCs produces exosomes with improved yield and enhanced therapeutic efficacy for cisplatin-induced acute kidney injury

Stem Cell Research & Therapy, Journal Year: 2020, Volume and Issue: 11(1)

Published: May 27, 2020

Exosomes derived from mesenchymal stem cells (MSC-exos) have been demonstrated with great potential in the treatment of multiple human diseases including acute kidney injury (AKI) by virtue their intrinsic cargoes. However, there are major challenges low yield and lack an established biomanufacturing platform to efficiently produce MSC-exos, thereby limiting therapeutic application. Here, we aimed establish a novel strategy MSC-exos hollow fiber bioreactor-based three-dimensional (3D) culture system evaluate efficacy 3D-exosomes (3D-exos) on AKI.Mesenchymal (MSCs) were isolated fresh umbilical cord cultured two-dimensional (2D) flasks. 2 × 108 MSCs inoculated into bioreactor for 3D culture. The supernatants collected every 1 or days isolating exosomes. 2D (2D-exos) cultures characterized transmission electron microscopy, nanoparticle tracking analysis, western blotting analysis exosome markers. exosomes seeded was compared, based protein quantification. 2D-exos 3D-exos investigated murine model cisplatin-induced AKI vivo vitro.3D did not significantly change surface markers MSCs, as well morphology, size, exosomal when compared those 2D-exos. Compared conventional culture, increased total production up 19.4-fold. more concentrated harvested (15.5-fold) than 2D-exos, which led higher collection efficiency system. In vivo, both alleviated evidenced improved renal function, attenuated pathological changes tubules, reduced inflammatory factors, repressed T cell macrophage infiltration. Impressively, effective Moreover, taken tubular epithelial (TECs) efficiency, exhibiting superior anti-inflammatory effect viability TECs vitro.In summary, our findings demonstrate that provides efficient continuous has enhanced AKI.

Language: Английский

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Neural Stem Cell Transplantation for Neurodegenerative Diseases

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3103 - 3103

Published: April 28, 2020

Neurodegenerative diseases are disabling and fatal neurological disorders that currently lack effective treatment. Neural stem cell (NSC) transplantation has been studied as a potential therapeutic approach appears to exert beneficial effect against neurodegeneration via different mechanisms, such the production of neurotrophic factors, decreased neuroinflammation, enhanced neuronal plasticity replacement. Thus, NSC may represent an strategy. To exploit NSCs’ potential, some their essential biological characteristics must be thoroughly investigated, including specific markers for subpopulations, allow profiling selection. Another key feature is secretome, which responsible regulation intercellular communication, neuroprotection, immunomodulation. In addition, NSCs properly migrate into central nervous system (CNS) integrate host circuits, enhancing neuroplasticity. Understanding modulating these aspects can us further NSCs. Recent progress in gene editing cellular engineering techniques opened up possibility modifying express select candidate molecules enhance effects. This review summarizes current knowledge regarding aspects, promoting development therapies could applied safely effectively clinical settings.

Language: Английский

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Extracellular vesicles as a drug delivery system: A systematic review of preclinical studies

Advanced Drug Delivery Reviews, Journal Year: 2021, Volume and Issue: 175, P. 113801 - 113801

Published: May 18, 2021

Language: Английский

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