Extracellular vesicles: a rising star for therapeutics and drug delivery

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: July 20, 2023

Abstract Extracellular vesicles (EVs) are nano-sized, natural, cell-derived that contain the same nucleic acids, proteins, and lipids as their source cells. Thus, they can serve natural carriers for therapeutic agents drugs, have many advantages over conventional nanocarriers, including low immunogenicity, good biocompatibility, blood – brain barrier penetration, capacity gene delivery. This review first introduces classification of EVs then discusses several currently popular methods isolating purifying EVs, EVs-mediated drug delivery, functionalization carriers. Thereby, it provides new avenues development EVs-based strategies in different fields medicine. Finally, highlights some challenges future perspectives with regard to clinical application EVs. Graphical

Language: Английский

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Bioengineered MSC-derived exosomes in skin wound repair and regeneration

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 27, 2023

Refractory skin defects such as pressure ulcers, diabetic and vascular ulcers represent a challenge for clinicians researchers in many aspects. The treatment strategies wound healing have high cost limited efficacy. To ease the financial psychological burden on patients, more effective therapeutic approach is needed to address chronic wound. MSC-derived exosomes (MSC-exosomes), main bioactive extracellular vesicles of paracrine effect MSCs, been proposed new potential cell-free regeneration. benefits MSC-exosomes include their ability promote angiogenesis cell proliferation, increase collagen production, regulate inflammation, finally improve tissue regenerative capacity. However, poor targeting easy removability from are major obstacles use clinical therapy. Thus, concept bioengineering technology has introduced modify exosomes, enabling higher concentrations construction particles greater stability with specific capability. biomaterials load may be promising strategy concentrate dose, create desired efficacy, maintain sustained release effect. beneficial role widely accepted; however, bioengineering-modified remains unclear. In this review, we attempt summarize applications modified challenges prospects bioengineered also discussed.

Language: Английский

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Engineering Bioactive M2 Macrophage‐Polarized, Anti‐inflammatory, miRNA‐Based Liposomes for Functional Muscle Repair: From Exosomal Mechanisms to Biomaterials

Small, Journal Year: 2022, Volume and Issue: 18(34)

Published: July 8, 2022

Severe inflammation and myogenic differentiation disorder are the major obstacles to skeletal muscle healing after injury. MicroRNAs (miRNAs) play an important role as regulatory molecules during process of healing, but detailed mechanism miRNA-mediated intercellular communication between myoblasts macrophages remains unclear. Here, it is reported that secrete miRNAs-enriched exosomes in inflammatory environment, through which miR-224 transferred into inhibit M2 polarization. Further data demonstrate WNT-9a may be a direct target for macrophage In turn, secretome M1 impairs promotes proliferation. Single-cell integration analysis suggests elevation exosome-derived caused by activation key factor E2F1 demonstrates RB/E2F1/miR-224/WNT-9a axis. vivo results show treatment with antagomir-224 or liposomes containing inhibitors suppresses fibrosis improves recovery. These findings indicate importance crosstalk via miRNA-containing regulation polarization differentiation/proliferation healing. This study provides strategy treating injury designing polarization-enabling anti-inflammatory miRNA-based bioactive material.

Language: Английский

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Low-intensity pulsed ultrasound promotes skeletal muscle regeneration via modulating the inflammatory immune microenvironment

International Journal of Biological Sciences, Journal Year: 2023, Volume and Issue: 19(4), P. 1123 - 1145

Published: Jan. 1, 2023

Background: Low-intensity pulsed ultrasound (LIPUS, a form of mechanical stimulation) can promote skeletal muscle functional repair, but lack mechanistic understanding its relationship and tissue regeneration limits progress in this field.We investigated the hypothesis that specific energy levels LIPUS mediates by modulating inflammatory microenvironment.Methods: To address these gaps, irritation was applied vivo for 5 min at two different intensities (30mW/cm 2 60mW/cm ) next 7 consecutive days, treatment begun 24h after air drop-induced contusion injury.In vitro experiments, three , 45mW/cm times introduction LPS RAW264.7.Then, we comprehensively assessed histological parameters injury mice phenotype shifting macrophages through molecular biological methods immunofluorescence analysis both vitro.Results: We reported therapy intensity exhibited most significant differences recovery contusion-injured mice.The comprehensive tests indirectly directly proved effectiveness recovery.Through vitro, found improvement attributable part to clearance M1 populations increase M2 subtypes with change macrophage-mediated factors.Depletion eliminated therapeutic effects LIPUS, indicating function result M2-shifted macrophage polarization.Moreover, M2-inducing were partially WNT pathway upregulating FZD5 expression enhancing β-catenin nuclear translocation vivo.The inhibition augment further verified our results.Conclusion: could significantly promoted from M2.The ability direct polarization may be beneficial target clinical many injuries diseases.

Language: Английский

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Research progress of exosomes in pathogenesis, diagnosis, and treatment of ocular diseases

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 24, 2023

Exosomes are natural extracellular vesicles with a diameter of 30–150 nm, which exist in biological fluids and contain biomolecules related to the parent cell, such as proteins, nucleic acids, lipids, etc. It has wide range functions, participates regulation important physiological pathological activities body. can be used biomarker for early diagnosis ocular diseases, potential therapeutic target, targeted drug carrier, high clinical application. In this paper, we summarized genesis mechanism, research application progress exosomes, focused on engineering strategy advantages disadvantages common exosome preparation methods. Systematically combed role exosomes corneal glaucoma, retinal provide reference further understanding pathogenesis, diagnosis, treatment diseases. Finally, opportunities challenges precision medicine. The extension field ophthalmology will help advance current diagnostic Tiny have huge potential.

Language: Английский

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Voluntary exercise sensitizes cancer immunotherapy via the collagen inhibition-orchestrated inflammatory tumor immune microenvironment

Cell Reports, Journal Year: 2024, Volume and Issue: 43(9), P. 114697 - 114697

Published: Aug. 31, 2024

Language: Английский

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The Revolution of exosomes: From biological functions to therapeutic applications in skeletal muscle diseases

Journal of Orthopaedic Translation, Journal Year: 2024, Volume and Issue: 45, P. 132 - 139

Published: March 1, 2024

Skeletal muscle diseases, a broad category encompassing myriad of afflictions such as acute injury and muscular dystrophies, pose significant health burden globally. These conditions often lead to weakness, compromised mobility, diminished quality life. In light this, innovative effective therapeutic strategies are fervently sought after. Exosomes, naturally extracellular vesicles with diameter 30–150 nm, pervade biological fluids. microscopic entities harbor host molecules, including proteins, nucleic acids, lipids, bearing resemblance their parent cells. The roles they play in the theater manifold, influencing crucial physiological pathological processes within organism. context skeletal potential extends beyond these roles, present promising target vehicle for targeted drug delivery. This potentially paves way clinical applications. review aims elucidate mechanisms underpinning exosome action, functions, strides made research application. A comprehensive exploration part played by exosomes repair regeneration is undertaken. addition, we delve into use landscape providing valuable reference deeper understanding applications this realm. concluding section encapsulates prospective avenues future hold, underscoring tremendous diminutive possess field diseases. Translational Potential Article. exosome's diverse functions translational diseases presented underscores applications, thus paving

Language: Английский

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Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: June 23, 2024

Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for it. The tumor microenvironment (TME) in pancreatic cancer, distinguished by fibrosis existence cancer-associated fibroblasts (CAFs), exerts pivotal influence on both advancement resistance to therapy. Recent advancements field engineered extracellular vesicles (EVs) offer novel avenues targeted therapy cancer. This study aimed develop EVs reprogramming CAFs modulating TME obtained from bone marrow mesenchymal stem cells (BMSCs) were loaded miR-138-5p anti-fibrotic agent pirfenidone (PFD) subjected surface modification integrin α5-targeting peptides (named IEVs-PFD/138) reprogram suppress their pro-tumorigenic effects. Integrin peptide enhanced CAF-targeting ability EVs. directly inhibited formation FERMT2-TGFBR1 complex, inhibiting TGF-β signaling pathway activation. In addition, proline-mediated collagen synthesis targeting FERMT2-PYCR1 complex. combination PFD synergistically promoted CAF suppressed pro-cancer effects CAFs. Preclinical experiments using orthotopic stroma-rich patient-derived xenograft mouse models yielded promising results. particular, IEVs-PFD/138 effectively reprogrammed remodeled TME, which resulted decreased pressure, gemcitabine perfusion, hypoxia amelioration, greater sensitivity chemotherapy. Thus, strategy developed this can improve chemotherapy outcomes. Utilizing as modulate represents approach

Language: Английский

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Exosomal miRNA-92a derived from cancer-associated fibroblasts promote invasion and metastasis in breast cancer by regulating G3BP2

Cellular Signalling, Journal Year: 2024, Volume and Issue: 119, P. 111182 - 111182

Published: April 17, 2024

Cancer-associated Fibroblasts (CAFs) exert a tumor-promoting effect in various cancers, including breast cancer. CAFs secrete exosomes containing miRNA and proteins, influencing the tumor microenvironment. In this study, we identified CAF-derived that transport functional miR-92a from to cells, thereby intensifying aggressiveness of downregulate expression G3BP2 cancer significant elevation levels was observed. Both vitro vivo experiments demonstrate enhances cell migration invasion by directly targeting G3BP2, functioning as miRNA. We validated RNA-binding proteins SNRPA facilitate transfer exosomal cells. The reduction protein releases TWIST1 into nucleus, promoting epithelial-mesenchymal transition (EMT) further exacerbating progression. Moreover, induces metastasis mice. Overall, our study reveals serves promoter cells reducing may represent potential novel marker for

Language: Английский

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Exercise potentially prevents colorectal cancer liver metastases by suppressing tumor epithelial cell stemness via RPS4X downregulation

Heliyon, Journal Year: 2024, Volume and Issue: 10(5), P. e26604 - e26604

Published: Feb. 24, 2024

BackgroundColorectal cancer (CRC) is the third most prevalent tumor globally. The liver common site for CRC metastasis, and involvement of a cause death in patients with late-stage CRC. Consequently, mitigating metastasis (CRLM) key to improving prognosis increasing survival. Exercise has been shown be an effective method many types. However, ability exercise inhibit CRLM yet thoroughly investigated.MethodsThe GSE157600 GSE97084 datasets were used analysis. A pan-cancer dataset which was uniformly normalized downloaded analyzed from UCSC database: TCGA, TARGET, GTEx (PANCAN, n = 19,131, G 60,499). Several advanced bioinformatics analyses conducted, including single-cell sequencing analysis, correlation algorithm, prognostic screen. microarray (TMA) as well cell/animal experiments are further validate results analysis.ResultsThe greatest variability found epithelial cells group. RPS4X generally upregulated all types CRC, while downregulated expression. lowered expression may prolong survival reduce metastasis. stemness marker-CD44 highly positively correlated knockdown reduced both vitro vivo.ConclusionRPS4X upregulation enhance increase odds through regulation RPS4X.

Language: Английский

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