Neutrophil-Derived Extracellular Vesicles for Facile Delivery of Diagnostic Agents to Tumor Microenvironments

ACS Applied Bio Materials, Год журнала: 2025, Номер unknown

Опубликована: Апрель 25, 2025

Targeted delivery of diagnostic and therapeutic agents to tumor microenvironments using nanoparticles improves the efficacy these reduces their unwarranted side effects. Numerous synthetic nanoparticle systems have been designed for this very purpose, but few translated clinically due poor efficacy-to-cost efficacy-to-toxicity ratios. Biological such as modified extracellular vesicles (EVs) that are likely lower toxicities also developed face challenges in clinical translation they primarily produced from cancerous cells/cell lines high batch-to-batch variability. To overcome issues, herein, we demonstrate EVs isolated neutrophils may be loaded with a specific agent (indocyanine green) facile manner within hours, agent-loaded retained vivo mouse tumors longer ∼5-fold increase retention when compared free hence facilitate short-term longitudinal imaging microenvironments. The use an individual's own cell-derived requiring minimal ex manipulations increases likelihood translating system into clinic.

Язык: Английский

---

DNA Nanomaterial‐Empowered Surface Engineering of Extracellular Vesicles

Advanced Materials, Год журнала: 2023, Номер 36(37)

Опубликована: Дек. 2, 2023

Abstract Extracellular vesicles (EVs) are cell‐secreted biological nanoparticles that critical mediators of intercellular communication. They contain diverse bioactive components, which promising diagnostic biomarkers and therapeutic agents. Their nanosized membrane‐bound structures innate ability to transport functional cargo across major barriers make them candidates as drug delivery vehicles. However, the complex biology heterogeneity EVs pose significant challenges for their controlled actionable applications in diagnostics therapeutics. Recently, DNA molecules with high biocompatibility emerge excellent blocks surface engineering EVs. The robust Watson–Crick base pairing resulting programmable nanomaterials provide EV precise structural customization adjustable physical chemical properties, creating unprecedented opportunities biomedical applications. This review focuses on recent advances utilization engineer surfaces. biology, function, summarized state‐of‐the‐art achievements isolation, analysis, based introduced. Finally, new frontiers discussed.

Язык: Английский

---

Mesenchymal stem cell-derived extracellular vesicles for treatment of bone loss within periodontitis in pre-clinical animal models: a meta-analysis

BMC Oral Health, Год журнала: 2023, Номер 23(1)

Опубликована: Сен. 29, 2023

Abstract Background Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent an effective and promising strategy for periodontitis, although studies remain pre-clinical. Herein, a meta-analysis was conducted to assess the efficacy of MSC-EVs in animal models periodontitis. Methods The PubMed, Web Science, Embase electronic databases were searched up Dec 2022 retrieve preclinical examining use periodontitis treatment. Meta-analyses sub-group analyses performed effect on Bone Volume/Total Volume (BV/TV) or distance between cementoenamel junction alveolar bone crest (CEJ-ABC) pre-clinical Results 11 published from Mar 2019 Oct met inclusion criteria. Overall, contributed periodontal regeneration inflammatory loss area due as represented by weighted mean difference (WMD) 14.07% (95% CI = 6.73, 21.41%, p < 0.001) BV/TV WMD -0.12 mm CI= -0.14, -0.11 mm, CEJ-ABC. However, sub-analysis suggested that there no significant CEJ-ABC with bioactive scaffolds without ( 0.60). Conclusions present study suggests may attractive therapy treatment within

Язык: Английский

---

Loading milk exosomes with urolithins boosts their delivery to the brain: Comparing the activity of encapsulated vs. free urolithins in SH-SY5Y neuroblastoma cells

Food Bioscience, Год журнала: 2024, Номер 61, С. 104888 - 104888

Опубликована: Авг. 6, 2024

The gut microbial-derived metabolites of ellagitannins and ellagic acid, urolithins (Uros) are well-established anti-cancer according to preclinical studies. However, their efficacy is limited in systemic tissues, including the brain, by phase-II metabolism. Exosomes (EXOs), extracellular vesicles involved cell signaling with ability cross blood-brain barrier (BBB), could protect polyphenols from Therefore, we loaded milk EXOs Uro-A, Uro-B or IsoUro-A evaluate brain delivery anticancer effects compared non-encapsulated Uros. In Sprague-Dawley rats, perfused tissue analyses UPLC-ESI-QTOF-MS showed higher Uro levels (∼3−4-fold) at 5 min following intravenous administration EXO-Uros Uros, except for Uro-B, using similar concentrations (17−30 μM). Experiments on neuroblastoma SH-SY5Y cells revealed dose-dependent antiproliferative all (0.3−1.2 μM), but not Uros (10 Flow cytometry indicated that only arrested cycle induced apoptosis. Finally, fluorescent-labeled selective inhibitors, primary endocytic pathway was be clathrin-dependent. Overall, encapsulating into promising enhancing activity.

Язык: Английский

---

Basic Guide for Approaching Drug Delivery with Extracellular Vesicles

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(19), С. 10401 - 10401

Опубликована: Сен. 27, 2024

Extracellular vesicles (EVs) are natural carriers of biomolecules that play a crucial role in cell-to-cell communication and tissue homeostasis under normal pathological conditions, including inflammatory diseases cancer. Since the discovery pro-regenerative immune-modulating properties EVs, EV-based therapeutics have entered clinical trials for conditions such as myocardial infarction autoimmune diseases, among others. Due to their unique advantages—such superior bioavailability, substantial packaging capacity, ability traverse biological barriers—EVs regarded promising platform targeted drug delivery. However, achieving sufficient accumulation therapeutic agents at target site necessitates larger quantity EVs per dose compared using standalone drugs. This challenge can be addressed by administering doses increasing dosage administration, or enhancing selective cells. In this review, we will discuss methods improve isolation purification approaches enhance cargo packaging—including proteins, RNAs, small-molecule drugs—and technologies displaying targeting ligands on surface facilitate improved targeting. Ultimately, guide applied development novel classes overcoming existing technological challenges.

Язык: Английский

---

Loading of extracellular vesicles with nucleic acids via hybridization with sponge-like lipid nanoparticles

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 13, 2024

Abstract The translation of cell-derived extracellular vesicles (EVs) into biogenic gene delivery systems is limited by relatively inefficient loading strategies. In this work, we describe the various nucleic acids small EVs via their spontaneous hybridization with preloaded non-lamellar liquid crystalline lipid nanoparticles (LCNPs) under physiological conditions, forming hybrid (HEVs). We correlate LCNPs’ topological characteristics propensity to fuse/aggregate and found that sponge (L 3 ) phases at pH 7.4 were particularly suitable induce a controlled process. State-of-the-art single-particle analysis techniques revealed L -based LCNPs interact EV subpopulations around 40% HEVs loaded genetic cargo. Importantly, study demonstrates membrane proteins remain accessible on HEV surfaces, intrinsic enzymatic activity unaffected after Finally, showed in vitro improved transfection efficiencies compared unhybridized LCNPs. summary, versatile platform holds potential for acid molecules native may help developing EV-based therapeutics. Teaser Topology influences behavior produces novel systems.

Язык: Английский

---

Suppression the glucose-induced ferroptosis in endothelial cells by 4OI-loading exosomes hydrogel for the treatment of diabetic foot ulcer

Chemical Engineering Journal, Год журнала: 2024, Номер 497, С. 154696 - 154696

Опубликована: Авг. 10, 2024

The prevalence of diabetic foot ulcer in individuals with diabetes is approximately 15%, and it frequently accompanied by vascular dysfunction infection. management challenges make the primary cause for amputation; however, underlying mechanisms remain poorly understood, thereby impeding advancement novel wound dressings medication. Herein, single-cell sequencing analysis revealed that ferroptosis induced high glucose levels endothelial cells (VECs) represents a significant molecular pathological feature (DFU) tissue. Furthermore, 4-Octyl itaconate (4OI) exhibited pronounced protective effect against VECs injury (HG), its involve mitigation HG-induced reactive oxygen species (ROS) through regulation Keap1/Nrf2/GPX4. For enhanced application, incubation at 37℃ was used to load 4OI into exosomes, which were subsequently encapsulated within an Alg-DA/GelMA-based hydrogel matrix. Remarkably, utilization 4OI-Exo-Gel not only expedited healing but also significantly improved overall quality DFU. In conclusion, these findings demonstrate, first time, remarkable ability enhance mitigating HG, provide evidence potential clinical translation 4OI-loaded exosomes therapy.

Язык: Английский

---

Surface-Enhanced Raman Scattering (SERS)-based biosensors for advanced extracellular vesicle detection: A review

Analytica Chimica Acta, Год журнала: 2024, Номер 1336, С. 343264 - 343264

Опубликована: Сен. 27, 2024

Язык: Английский

---

Investigation of Lipid-PEG Anchorage of Proteins onto Mesenchymal Stem Cell Derived Extracellular Vesicles for Intracellular Delivery: A Quantitative Assessment

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Авг. 29, 2024

Abstract Despite biomolecule delivery is a natural function of Extracellular Vesicles (EVs), loading exogenous macromolecules such as proteins into EVs remains major challenge limiting their interest convincing protein systems for health applications. In this context, lipid-anchorage cargo EV membrane recently emerged promising option to enable vectorization cells. Nevertheless, was not explored intracellular delivery, and further characterization the critical parameters governing association lipid-anchored still needed confirm relevance anchorage strategy. Therefore, in work, we have sought identify these precise quantitative manner, working with bulk single nanoparticle analysis methods capacity subsequent delivery. Incubation temperature, concentration Lipid Anchor (LA) structure (lipid nature PEG size) appeared factors influencing maximal capacity. Precise control enabled load close saturation without hindering cellular Interestingly, evidenced that isolation process influenced association. Structural properties LA only protein/EV association, but also its different carcinoma cell lines. By thoroughly characterizing Lipid-PEG-protein anchorage, study evidences tunable controllable approach efficient Graphical abstract

Язык: Английский

---

Isolation and characterization of medicinal plant-based extracellular vesicles as nano delivery systems for ascorbic acid

Journal of Microencapsulation, Год журнала: 2024, Номер unknown, С. 1 - 12

Опубликована: Дек. 23, 2024

Plant-derived extracellular vesicles (EVs) are natural nanovesicles for drug delivery. This study isolated and characterised EVs from medicinal plants as delivery vehicles.

Язык: Английский

---