Current Strategies for Exosome Cargo Loading and Targeting Delivery

Cells, Год журнала: 2023, Номер 12(10), С. 1416 - 1416

Опубликована: Май 17, 2023

Extracellular vesicles (EVs) such as ectosomes and exosomes have gained attention promising natural carriers for drug delivery. Exosomes, which range from 30 to 100 nm in diameter, possess a lipid bilayer are secreted by various cells. Due their high biocompatibility, stability, low immunogenicity, favored cargo carriers. The membrane of also offers protection against degradation, making them desirable candidate However, loading into remains be challenge. Despite strategies incubation, electroporation, sonication, extrusion, freeze–thaw cycling, transfection that been developed facilitate loading, inadequate efficiency still persists. This review an overview current delivery using summarizes recent approaches small-molecule, nucleic acid, protein drugs exosomes. With insights these studies, we provide ideas more efficient effective molecules

Язык: Английский

---

Exosomes: compositions, biogenesis, and mechanisms in diabetic wound healing

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 5, 2024

Abstract Diabetic wounds are characterized by incomplete healing and delayed healing, resulting in a considerable global health care burden. Exosomes lipid bilayer structures secreted nearly all cells express characteristic conserved proteins parent cell-associated proteins. harbor diverse range of biologically active macromolecules small molecules that can act as messengers between different cells, triggering functional changes recipient thus endowing the ability to cure various diseases, including diabetic wounds. accelerate wound regulating cellular function, inhibiting oxidative stress damage, suppressing inflammatory response, promoting vascular regeneration, accelerating epithelial facilitating collagen remodeling, reducing scarring. from tissues or potentially possess functions varying levels promote healing. For example, mesenchymal stem cell-derived exosomes (MSC-exos) have favorable potential field due their superior stability, permeability, biocompatibility, immunomodulatory properties. Exosomes, which derived skin components, modulate inflammation regeneration key turn promotes Therefore, this review mainly emphasizes roles mechanisms sources, represented MSCs improving A deeper understanding therapeutic will yield promising candidates perspectives for management.

Язык: Английский

---

Milk Exosomes: Next-Generation Agents for Delivery of Anticancer Drugs and Therapeutic Nucleic Acids

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 10194 - 10194

Опубликована: Июнь 15, 2023

Exosomes are nanovesicles 40–120 nm in diameter secreted by almost all cell types and providing humoral intercellular interactions. Given the natural origin high biocompatibility, potential for loading various anticancer molecules therapeutic nucleic acids inside, surface modification possibility targeted delivery, exosomes considered to be a promising means of delivery cultures experimental animal organisms. Milk is unique source available semi-preparative preparative quantities. highly resistant harsh conditions gastrointestinal tract. In vitro studies have demonstrated that milk an affinity epithelial cells, digested cells endocytosis mechanism, can used oral delivery. With exosome membranes containing hydrophilic hydrophobic components, loaded with lipophilic drugs. This review covers number scalable protocols isolating purifying from human, cow, horse milk. Additionally, it considers passive active methods drug into exosomes, as well modifying functionalizing specific more efficient target cells. addition, approaches visualize determine cellular localization bio-distribution tissues. conclusion, we outline new challenges studying generation agents.

Язык: Английский

---

Small extracellular vesicles: Yields, functionalization and applications in diabetic wound management

Deleted Journal, Год журнала: 2023, Номер 1(4)

Опубликована: Окт. 1, 2023

Abstract Diabetic wounds have imposed a significant burden on both patients and society with prolonged healing processes hindered by dysfunctional skin repair cells. Small extracellular vesicles (sEVs), as the important media for intercellular communications, show promising therapeutic potential in treating diabetic restoring cellular functions. However, low yields limited bio‐function of sEVs greatly challenge their large‐scale clinical use. Here, we briefly overview biogenesis uptake sEVs, emphasize current advances improving optimizing function engineering approaches, summarize applications engineered wound treatment. Furthermore, undissolved issues during transformation are also discussed. This critical review aims to provide meaningful guidance future management wounds.

Язык: Английский

---

Targeting delivery of miR-146a via IMTP modified milk exosomes exerted cardioprotective effects by inhibiting NF-κB signaling pathway after myocardial ischemia-reperfusion injury

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 1, 2024

Abstract Reperfusion therapy is critical for saving heart muscle after myocardial infarction, but the process of restoring blood flow can itself exacerbate injury to myocardium. This phenomenon known as ischemia-reperfusion (MIRI), which includes oxidative stress, inflammation, and further cell death. microRNA-146a (miR-146a) play a significant role in regulating immune response has been studied its potential impact on improvement function injury. However, delivery miR-146a specific efficient manner remains challenge extracellular RNAs are unstable rapidly degraded. Milk exosomes (MEs) have proposed ideal platform miRNA-based they protect miRNAs from RNase degradation. In this study, effects containing MEs (MEs-miR-146a) cardiac were examined rat model MIRI. To enhance targeting MEs-miR-146a site injury, ischemic myocardium-targeted peptide IMTP was modified onto surfaces, whether could exert better therapeutic by echocardiography, indicators levels inflammatory factors. Furthermore, expressions mediated NF-κB signaling pathway-related proteins detected western blotting qRT-PCR elucidate mechanisms. MiR-146 mimics successfully loaded into electroporation at square wave 1000 V voltage 0.1 ms pulse duration. be up-taken cardiomyocytes protected cells oxygen glucose deprivation/reperfusion induced damage vitro. Oral administration decreased tissue apoptosis expression factors improved The level myocardium tissues significantly increased MEs-miR-146a, higher than that group. addition, intravenous injection enhanced heart, function, reduced suppressed inflammation MIRI, more effective treatment. Moreover, protein IRAK1, TRAF6 p-p65. Therefore, exerted their anti-inflammatory effect inhibiting IRAK1/TRAF6/NF-κB pathway. Taken together, our findings suggested may promising strategy treatment MIRI with outcome modification peptide, expected applied clinical practice future.

Язык: Английский

---

Opportunities and challenges of engineered exosomes for diabetic wound healing

Giant, Год журнала: 2024, Номер 18, С. 100251 - 100251

Опубликована: Март 6, 2024

The treatment of diabetic wounds is a major challenge faced by the medical system, and there growing interest in developing innovative therapies to accelerate wound healing. Regenerative medicine with cells has shown promising potential skin repair, regenerative properties primarily attributed paracrine effects secreted products, including exosomes. Compared cell-based approaches, using exosomes as cell-free therapy for chronic several advantages. Exosomes can regulate intercellular communication releasing their contents, mRNA, miRNA, lipids, proteins, which further promote are well explored biomedical application owing advantages such biocompatibility low immunogenicity. However, common method exosome administration through injection, but due rapid clearance rate body, maintaining necessary therapeutic concentration around challenging. Therefore, it develop new biocompatible scaffold carrier extracellular vesicles, allowing them sustain at non-healing sites continuously Engineered kinds modified internal treated molecules, surface decoration or delivered engineered platform. In addition, some researchers have processed exosomes, known decoration, delivery platforms. regular greater promoting this review, we summarize molecular mechanisms from different sources varying modifications Advantages limitations repair were also discussed. Finally, highlight challenges future development directions translating our knowledge into clinical practice.

Язык: Английский

---

Targeting Signalling Pathways in Chronic Wound Healing

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 50 - 50

Опубликована: Дек. 19, 2023

Chronic wounds fail to achieve complete closure and are an economic burden healthcare systems due the limited treatment options constant medical attention. characterised by dysregulated signalling pathways. Research has focused on naturally derived compounds, stem-cell-based therapy, small molecule drugs, oligonucleotide delivery nanoparticles, exosomes peptide-based platforms. The phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT), Wingless-related integration (Wnt)/β-catenin, transforming growth factor-β (TGF-β), nuclear factor erythroid 2–related 2 (Nrf2), Notch hypoxia-inducible 1 (HIF-1) pathways have critical roles in wound healing modulating inflammatory, proliferative remodelling phases. Moreover, several regulators of were demonstrated be potential targets. In this review, current research targeting under chronic conditions will discussed together with implications for future studies.

Язык: Английский

---

Potential therapeutic effects of milk-derived exosomes on intestinal diseases

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Дек. 20, 2023

Exosomes are extracellular vesicles with the diameter of 30 ~ 150 nm, and widely involved in intercellular communication, disease diagnosis drug delivery carriers for targeted therapy. Therapeutic application exosomes as is limited due to lack sources methods obtaining adequate exosomes. Milk contains abundant exosomes, several studies have shown that milk-derived play crucial roles preventing treating intestinal diseases. In this review, we summarized biogenesis, secretion structure, current novel used extraction identification well discussed role diseases, such inflammatory bowel disease, necrotizing enterocolitis, colorectal cancer, ischemia reperfusion injury by regulating immune homeostasis, restoring gut microbiota composition improving structure integrity, alleviating conditions oxidative stress, cell apoptosis inflammation, reducing mitochondrial reactive oxygen species (ROS) lysosome accumulation both humans animals. addition, future prospects standardization milk exosome production platform obtain higher concentration purity, complete derived from milk. Several vivo clinical needed establish an effective efficient system, promote its treatment various diseases

Язык: Английский

---

Nebulized milk exosomes loaded with siTGF-β1 ameliorate pulmonary fibrosis by inhibiting EMT pathway and enhancing collagen permeability

Journal of Nanobiotechnology, Год журнала: 2024, Номер 22(1)

Опубликована: Июль 23, 2024

Abstract Pulmonary Fibrosis (PF) is a fatal disease in the interstitial lung associated with high mortality, morbidity, and poor prognosis. Transforming growth factor-β1 (TGF-β1) fibroblast-activating protein that promotes fibrous diseases. Herein, an inhalable system was first developed using milk exosomes (M-Exos) encapsulating siRNA against TGF-β1 (MsiTGF-β1), their therapeutic potential for bleomycin (BLM)-induced PF investigated. M-siTGF-β1 introduced into lungs of mice through nebulization. The collagen penetration effect lysosomal escape ability were verified vitro. Inhaled MsiTGF-β1 notably alleviated inflammatory infiltration, attenuated extracellular matrix (ECM) deposition, increased survival rate by 4.7-fold. protected tissue from BLM toxicity efficiently delivering specific to lungs, leading mRNA silencing epithelial mesenchymal transition pathway inhibition. Therefore, offers promising avenue intervention fibrosis-related disorders.

Язык: Английский

---

Engineering Approaches for Exosome Cargo Loading and Targeted Delivery: Biological versus Chemical Perspectives

ACS Biomaterials Science & Engineering, Год журнала: 2024, Номер 10(10), С. 5960 - 5976

Опубликована: Июнь 28, 2024

Exosomes are nanoscale membrane bound vesicles secreted by almost all types of cells. Their unique attributes, such as minimal immunogenicity and compatibility with biological systems, make them novel carriers for drug delivery. These native exosomes harbor proteins, nucleic acids, small molecule compounds, fluorogenic agents. Moreover, through a combination chemical bioengineering methodologies, tailored to transport precise therapeutic payloads designated cells or tissues. In this review, we summarize the strategies exosome modification loading modalities in engineered exosomes. addition, provide an overview advances use targeted Lastly, discuss merits limitations chemically versus bioengineered exosome-mediated target therapies. insights offer additional options refining pharmaceutical development hold promise expediting successful translation from bench bedside.

Язык: Английский

---