Sparstolonin B potentiates the antitumor activity of nanovesicle-loaded drugs by suppressing the phagocytosis of macrophages in vivo DOI Creative Commons
Yuefeng Zhang,

Zuo Mou,

Wei Song

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Dec. 18, 2024

Extracellular vesicles (EVs) and extruded nanovesicles (ENVs) are promising (NVs) for drug delivery. However, the application of these NVs is strongly hindered by their short half-life in circulation. Macrophages (Mφs) liver spleen contribute to rapid depletion NVs, but underlying mechanism unclear. By collecting supernatant PANC-1 cells squeezing cells, EVs ENVs derived from were prepared via ultracentrifugation. subsequently identified western blot, particle size measurement, electron microscopy. The distribution mouse bodies was observed with a live animal imaging system. Liver Mφs extracted isolated after administered, transcriptome profiling applied determine differentially expressed genes (DEGs). siRNAs targeting interested designed synthesized. In vitro experiments, transfected siRNA or treated corresponding inhibitor, which NV uptake recorded. Doxorubicin (DOX) encapsulated using an ultrasound method. cell-derived tumors established nude mice vivo, inhibitor pretreatment no treatment administered before intravenous injection ENVs-DOX, therapeutic efficacy ENVs-DOX evaluated. first identified. After injection, most engulfed spleen. Seven interest selected sequencing validated RT‒PCR. These results confirmed that TLR2 signaling pathway responsible phagocytosis. siTLR2 its sparstolonin B (SpB) significantly inhibited internalization downregulated activity pathway. accumulation vivo SpB 40 min ultimately delaying tumor progression. plays crucial role sequestration Mφs. A novel antiphagocytic strategy inhibits clearance prolongs thereby improving delivery efficiency,

Language: Английский

Current knowledge of hybrid nanoplatforms composed of exosomes and organic/inorganic nanoparticles for disease treatment and cell/tissue imaging DOI Creative Commons
Fatemeh Soltanmohammadi,

Adel Mahmoudi Gharehbaba,

Ali Rajabi Zangi

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 178, P. 117248 - 117248

Published: Aug. 3, 2024

Exosome-nanoparticle hybrid nanoplatforms, can be prepared by combining exosomes with different types of nanoparticles. The main purpose nanoparticles is to overcome the limitations using each them as drug delivery systems. Using for has some limitations, such high immunogenicity, poor cellular uptake, low biocompatibility, cytotoxicity, stability, and rapid clearance immune cells. However, systems also its own drawbacks, encapsulation efficiency, production yield, inability load large molecules. These addressed utilizing nanoplatforms. Additionally, use allows targeted within system. Exosome-inorganic/organic may used both therapy diagnosis in future. This lead development personalized medicine there are a few challenges associated this. Surface modifications, adding functional groups, surface charge adjustments, preparing desired size crucial possibility exosome-nanoparticle hybrids. Additional successful implementation platforms medical treatments diagnostics include scaling up manufacturing process ensuring consistent quality reproducibility across various batches. review focuses on discusses preparation loading methods these Furthermore, potential applications nanocarriers drug/gene delivery, disease treatment diagnosis, cell/tissue imaging explained.

Language: Английский

Citations

15

Extracellular vesicles encapsulated with caspase-1 inhibitor ameliorate experimental autoimmune myasthenia gravis through targeting macrophages DOI Creative Commons
Yang Zhou,

Tong Du,

Chunlin Yang

et al.

Journal of Controlled Release, Journal Year: 2023, Volume and Issue: 364, P. 458 - 472

Published: Nov. 8, 2023

Cysteinyl aspartate-specific proteinase-1 (caspase-1) is a multifunctional inflammatory mediator in many inflammation-related diseases. Previous studies show that caspase-1 inhibitors produce effective therapeutic outcomes rat model of myasthenia gravis. However, tissue toxicity and unwanted off-target effects are the major disadvantages limiting their clinical application as agents. This study shows dendritic cell-derived extracellular vesicles (EVs) loaded with inhibitor (EVs-VX-765) phagocytized mainly by macrophages, precisely expressed macrophages. Furthermore, EVs-VX-765 demonstrates excellent through macrophage-dependent mechanism, it notably inhibits level interleukin-1β subsequently Th17 response germinal center (GC) reactions. In addition, better than routine doses VX-765, although drug loading much lower doses, consequently reducing toxicity. conclusion, this study's findings suggest EV-mediated delivery for treating gravis promising applications.

Language: Английский

Citations

14

Unraveling the Multifaceted Roles of Extracellular Vesicles: Insights into Biology, Pharmacology, and Pharmaceutical Applications for Drug Delivery DOI Open Access
Ali Al-Jipouri, Àuria Eritja, Milica Božić

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 25(1), P. 485 - 485

Published: Dec. 29, 2023

Extracellular vesicles (EVs) are nanoparticles released from various cell types that have emerged as powerful new therapeutic option for a variety of diseases. EVs involved in the transmission biological signals between cells and regulation processes, highlighting them potential novel targets/platforms therapeutics intervention and/or delivery. Therefore, it is necessary to investigate aspects EVs' biogenesis, biodistribution, metabolism, excretion well safety/compatibility both unmodified engineered upon administration different pharmaceutical dosage forms delivery systems. In this review, we summarize current knowledge essential physiological pathological roles organs organ We provide an overview regarding application targets, therapeutics, drug platforms. also explore approaches implemented over years improve specific EV products routes.

Language: Английский

Citations

11

Macrophage Functions in Psoriasis: Lessons from Mouse Models DOI Open Access
Katarzyna Nazimek, Krzysztof Bryniarski

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5306 - 5306

Published: May 13, 2024

Psoriasis is a systemic autoimmune/autoinflammatory disease that can be well studied in established mouse models. Skin-resident macrophages are classified into epidermal Langerhans cells and dermal involved innate immunity, orchestration of adaptive maintenance tissue homeostasis due to their ability constantly shift phenotype adapt the current microenvironment. Consequently, both macrophage populations play dual roles psoriasis. In some circumstances, pro-inflammatory activated trigger psoriatic inflammation, while other cases anti-inflammatory stimulation results amelioration disease. These features make interesting candidates for modern therapeutic strategies. Owing significant progress knowledge, our review article summarizes achievements indicates future research directions better understand function

Language: Английский

Citations

3

Quality Control of Fetal Wharton’s Jelly Mesenchymal Stem Cells-Derived Small Extracellular Vesicles DOI Creative Commons

Illayaraja Krishnan,

Chiew Yong Ng, Li Ting Kee

et al.

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 1807 - 1820

Published: Feb. 1, 2025

Background: Quality control (QC) is an important element in ensuring drug substances' safety, efficacy, and quality. The dosing regimen for sEVs can be the form of protein concentration or number particles based on results a series quality controls applied as in-process control. Methods: Wharton's Jelly Mesenchymal Stem Cells (WJMSCs) were isolated from four independent umbilical cord samples characterized following International Society Cellular Therapy (ISCT) guidelines. Small extracellular vesicles (sEVs) separately these WJMSCs using Tangential Flow Filtration (TFF) method per Minimal Information Studies Extracellular Vesicles (MISEV2018) Each concentrated sEV preparation was standardized its purity determined by ratio to concentration. Results: All passed (MSCs) characterization QC tests. Qualitatively, EVs-positive markers (CD63 TSG101) intact bilipid membrane detected all preparations. Quantitatively, particle concentrations revealed that preparations "impure" with < 1.5 × 10 9 particles/μg protein. Albumin co-isolated Conclusion: In short, individual pooled deemed due albumin co-isolation TFF method. For therapeutic development, it essential report EV results. Keywords: control, cord, jelly mesenchymal stem cells, tangential flow filtration, small vesicles,

Language: Английский

Citations

0

Therapeutic Potential of Extracellular Vesicles in Oral Inflammation DOI Open Access
Yan Yan Farm,

Bing Huan Chuah,

Jia Xian Law

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3031 - 3031

Published: March 26, 2025

The therapeutic potential of extracellular vesicles (EVs) in reducing oral inflammation is thoroughly examined this review, with an emphasis on gingivitis, periodontitis, and mucositis. It explains the complex relationship between microbial dysbiosis host immune responses aetiology inflammation. Pathophysiological mechanisms periodontitis are examined, emphasising roles played by periodontal pathogens inflammatory mediators disease's chronic course systemic effects. Preclinical research providing new evidence that EVs originating from various cellular sources control cell dynamics towards a pro-healing phenotype, promote tissue regeneration, have immunomodulatory qualities. EV-based therapies appear to be promising technique benefits over traditional methods for treatment illnesses specifically altering signalling pathways. This review highlights improve patient outcomes health emphasises need additional clinical clarify efficacy underlying therapy.

Language: Английский

Citations

0

Harnessing Extracellular Vesicles for Targeted Drug Delivery in Ovarian Cancer DOI Creative Commons
Jang‐Hyuk Yun,

Yoo Rim Noh,

Seongkyeong Yoo

et al.

Pharmaceutics, Journal Year: 2025, Volume and Issue: 17(4), P. 528 - 528

Published: April 17, 2025

Ovarian cancer remains one of the most lethal gynecologic malignancies, primarily due to late-stage diagnosis, high recurrence rates, and development chemoresistance. Although targeted therapies have improved patient outcomes, their efficacy is often limited by off-target toxicity acquired drug resistance. Extracellular vesicles (EVs), nanoscale naturally released cells, emerged as promising carriers for precision delivery. This review provides a comprehensive overview recent advances in EV-based therapeutic strategies ovarian cancer, including delivery chemotherapeutic agents, nucleic acid therapeutics, immunomodulatory molecules. We further explore innovative engineering approaches enhance targeting specificity, such surface modification, cell source selection, biomaterial integration, magnetic nanoparticle-assisted Key translational challenges bringing clinical application are also addressed. Collectively, these insights underscore transformative potential platforms advancing personalized treatment cancer.

Language: Английский

Citations

0

Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function DOI
Soazig Le Lay, Philipp E. Scherer

Cell Reports, Journal Year: 2025, Volume and Issue: 44(6), P. 115732 - 115732

Published: May 22, 2025

Language: Английский

Citations

0

All but Small: miRNAs from Wharton’s Jelly-Mesenchymal Stromal Cell Small Extracellular Vesicles Rescue Premature White Matter Injury after Intranasal Administration DOI Creative Commons
Vera Tscherrig,

Marel Steinfort,

Valérie Haesler

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 543 - 543

Published: March 19, 2024

White matter injury (WMI) is a common neurological issue in premature-born neonates, often causing long-term disabilities. We recently demonstrated key beneficial role of Wharton’s jelly mesenchymal stromal cell-derived small extracellular vesicles (WJ-MSC-sEVs) microRNAs (miRNAs) WMI-related processes vitro. Here, we studied the functions WJ-MSC-sEV miRNAs vivo using preclinical rat model premature WMI. Premature WMI was induced pups through inflammation and hypoxia-ischemia. Small EVs were purified from culture supernatant human WJ-MSCs. The capacity WJ-MSC-sEV-derived to decrease microglia activation promote oligodendrocyte maturation evaluated by knocking down (k.d) DROSHA WJ-MSCs, releasing sEVs containing significantly less mature miRNAs. MSC-sEVs intranasally administrated 24 h upon reached brain within 1 h, remained detectable for at least reduced microglial activation, promoted maturation. k.d WJ-MSCs lowered therapeutic capabilities experimental Our results strongly indicate relevance abilities WJ-MSC-sEVs vivo, opening path clinical application.

Language: Английский

Citations

2

Hypotensive drugs mitigate the high-sodium diet-induced pro-inflammatory activation of mouse macrophages in vivo DOI Open Access
Martyna Cieślik,

Spencer Strobel,

Paweł Bryniarski

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116648 - 116648

Published: April 26, 2024

Nowadays, there is an increasing emphasis on the need to alleviate chronic inflammatory response effectively treat hypertension. However, are still gaps in our understanding how achieve this. Therefore, research interaction of antihypertensive drugs with immune system extremely interesting, since their therapeutic effect could partly result from amelioration hypertension-related inflammation, which macrophages seem play a pivotal role. Thus, current comprehensive studies have investigated impact repeatedly administered hypotensive (captopril, olmesartan, propranolol, carvedilol, amlodipine, verapamil) macrophage functions innate and adaptive immunity, as well if drug-induced effects affected by high-sodium diet (HSD), one key environmental risk factors Although assayed medications increased generation reactive oxygen nitrogen intermediates standard fed donors, they reversed HSD-induced enhancing oxidative burst secretion pro-inflammatory cytokines. On other hand, some phagocytic activity expression surface markers involved antigen presentation, translated into enhanced ability activate B cells for antibody production. Moreover, augmented function effector phase contact hypersensitivity reaction, but suppressed sensitization cell-mediated under HSD conditions. Our findings contribute recognition mechanisms, excessive sodium intake affects hypertensive individuals, provide evidence that mitigate most adverse effects, suggesting additional protective activity.

Language: Английский

Citations

2