Dual-Targeting of PDPN-Expressing Synovial Fibroblasts and Macrophages via CLEC-2-Engineered Exosomes for Osteoarthritis Therapy DOI Creative Commons
Bo Yu,

Rui Peng,

Zitao Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Synovitis is often associated with osteoarthritis (OA) and may even precede the onset of OA symptoms. Although targeting synovial inflammation has shown therapeutic promise in OA, synovium's heterogeneous composition, multiple cell types contributing to inflammatory response, indicates that focusing on a single population not provide most favorable results. This investigation employed scRNA-seq tissues from both human murine sources, revealing fibroblasts macrophages expressing high levels Podoplanin (PDPN). These cells constitute approximately 70% total display pro-inflammatory properties. Drawing inspiration unique interaction between PDPN CLEC-2, we engineered mesenchymal stromal cell-derived exosomes overexpress CLEC-2 (ExosomeCLEC-2) encapsulated liquiritigenin-loaded poly (lactic-co-glycolic acid) (PLGA) within ExosomeCLEC-2 membrane (EMCLEC-2), creating PDPN-targeting nanoparticle system called EMCLEC-2-PLGA-liquiritigenin (EMPL). Remarkably, EMPL concurrently targets PDPNhigh macrophages, exhibiting anti-inflammatory effects both vitro in vivo, preventing cartilage degeneration traumatic model. In summary, our research highlights potential developing platform can target mitigate processes offering novel promising strategy for treatment osteoarthritis.

Язык: Английский

Exosomes as Therapeutic and Diagnostic Tools: Advances, Challenges, and Future Directions DOI

Tejas C. Jangam,

Sharav Desai, Vipul P. Patel

и другие.

Cell Biochemistry and Biophysics, Год журнала: 2025, Номер unknown

Опубликована: Март 24, 2025

Язык: Английский

Процитировано

2
The Potential of Mesenchymal Stem Cell-Derived Exosomes to Treat Diabetes Mellitus DOI Creative Commons
Ju-El Kim, Jong Won Lee, Gi Doo

и другие.

Biomimetics, Год журнала: 2025, Номер 10(1), С. 49 - 49

Опубликована: Янв. 14, 2025

Diabetes mellitus (DM) is a fatal metabolic disease characterized by persistent hyperglycemia. In recent studies, mesenchymal stem cell (MSC)-derived exosomes, which are being investigated clinically as cell-free therapy for various diseases, have gained attention due to their biomimetic properties that closely resemble natural cellular communication systems. These MSC-derived exosomes inherit the regenerative and protective effects from MSCs, inducing pancreatic β-cell proliferation inhibiting apoptosis, well ameliorating insulin resistance suppressing release of inflammatory cytokines. Consequently, attracted novel treatment DM an alternative therapy. this review, we will introduce potential discussing studies used treat DM, shown therapeutic in both type 1 2 DM.

Язык: Английский

Процитировано

1
Multifunctional extracellular vesicles and edaravone-loaded scaffolds for kidney tissue regeneration by activating GDNF/RET pathway DOI Creative Commons
Seung Yeon Lee, Jeong Min Park, Won‐Kyu Rhim

и другие.

Nano Convergence, Год журнала: 2024, Номер 11(1)

Опубликована: Окт. 26, 2024

With the severity of chronic kidney disease worldwide, strategies to recover renal function via tissue regeneration provide alternatives replacement therapy. To exclude side effects from direct cell transplantation, extracellular vesicles (EVs) are great substitutes representing paracrine signaling. build three-dimensional structures for implantation into 5/6 nephrectomy model by incorporating bioactive materials, including multifunctional EVs (mEVs), porous PMEZE/mEV scaffolds were developed in combination with edaravone (EDV; E) and mEV based on PMEZ PLGA (P), MH-RA (M), ECM (E), ZnO-ALA (Z). The oxygen free radical scavenger EDV was incorporated induce tubular regeneration. mEVs engineered serve regenerative activities a two SDF-1α overexpressed tonsil-derived mesenchymal stem cells (sEVs) intermediate mesoderm (IM) during differentiation progenitor (dEVs). displayed beneficial facilitating migration inducing surrounding cells, improved regulating GDNF/RET pathway their downstream genes. promotion MSC recruitment confirmed sEV particles number dependently, regulation effect its enhanced elucidated using vitro analysis. tubules additionally demonstrated through increased expression aquaporin-1 (AQP-1) cadherin-16 (CDH16) proximal tubules, calbindin PAX2 distal defect model. these, structural functional recovery achieved mice

Язык: Английский

Процитировано

3
Sustained Release of HIF-2α Inhibitors Using Biodegradable Porous Silicon Carriers for Enhanced Immunogenic Cell Death of Malignant Merkel Cell Carcinoma DOI
Jinsil Seong, Minju Kim, Jounghyun Yoo

и другие.

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Янв. 20, 2025

Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine skin cancer with limited treatment options, often associated polyomavirus (MCPyV) and marked by hypoxic tumor microenvironments that promote resistance to therapies. Belzutifan, an FDA-approved hypoxia-inducible factor-2α (HIF-2α) inhibitor, has shown promise in inhibiting growth; however, its clinical efficacy hindered low solubility, rapid clearance, bioavailability. In this study, we present strategy using porous silicon (pSi) microparticles nanoparticles as carriers for the sustained delivery of benzoate MCC cells. The pSi were engineered securely encapsulate gradually release belzutifan, overcoming limitations free drug administration. Microparticles provided extracellular release, while enabled efficient intracellular delivery, enhancing HIF-2α inhibition. Moreover, use biodegradable particles enables long-term consistent belzutifan over 10 days vitro single dose administration microenvironment, rapidly deactivated within 1 day postadministration. studies demonstrated significant immunogenic death (ICD) cells, cytosolic localization HMGB1 elevated expression pro-inflammatory cytokines well strong upregulation TLR9. Particularly, increased TLR9 both lines carrier reinforces immune activation through toll-like receptor signaling, innate adaptive responses microenvironment. These findings indicate not only enhance belzutifan's stability profile also amplify antitumor Our results suggest belzutifan-loaded offer potent targeted therapeutic MCC, potentially addressing key challenges immunotherapy combining inhibition robust activation. This platform highlights universal utility pSi-based systems advance implications broader

Язык: Английский

Процитировано

0
Dual-targeting of PDPN-expressing synovial fibroblasts and macrophages via CLEC-2-engineered exosomes for osteoarthritis therapy DOI
Bo Yu,

Rui Peng,

Zitao Liu

и другие.

Chemical Engineering Journal, Год журнала: 2025, Номер unknown, С. 160628 - 160628

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Injured Cardiac Tissue-Targeted Delivery of TGFβ1 siRNA by FAP Aptamer-Functionalized Extracellular Vesicles Promotes Cardiac Repair DOI Creative Commons

Ji-Young Kang,

Dasom Mun,

Malgeum Park

и другие.

International Journal of Nanomedicine, Год журнала: 2025, Номер Volume 20, С. 2575 - 2592

Опубликована: Март 1, 2025

Small-interfering RNA (siRNA) therapy holds significant potential for treating cardiac injury; however, its clinical application is constrained by poor blood stability and insufficient cellular uptake. Extracellular vesicles (EVs) have emerged as an effective delivery system siRNA in vivo; but their lack of specific cell or tissue-targeting ability remains a major challenge. Thus, we aimed to develop EV-based capable targeted therapeutic injured tissue repair. To identify fibroblast activation protein (FAP) target tissue, analyzed tissues from patients with heart failure angiotensin II (Ang II)-treated mice. Injured EVs were developed embedding cholesterol-conjugated FAP aptamer, which specifically targets FAP, onto human serum-derived (hEV). Our findings revealed that upregulated after injury, highlighting tissues. We successfully aptamer-functionalized hEV (hEV@FAP) confirmed typical EV characteristics, including morphology, size distribution, zeta potential, marker expression. In addition, hEV@FAP demonstrated high targeting selectivity FAP-positive regions both vitro vivo. treat loaded TGFβ1 (siTGFβ1), identified molecular Ang II-treated mice, intravenous administration hEV@FAP-siTGFβ1 effectively reduced II-induced expression tissues, attributed the protective capabilities hEV@FAP. Consequently, significantly improved function, myocardial fibrosis, decreased cardiomyocyte cross-sectional area (P < 0.05) without inducing systemic toxicity. represents novel approach providing promising nanomedicine

Язык: Английский

Процитировано

0
Dual-Targeting of PDPN-Expressing Synovial Fibroblasts and Macrophages via CLEC-2-Engineered Exosomes for Osteoarthritis Therapy DOI Creative Commons
Bo Yu,

Rui Peng,

Zitao Liu

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Synovitis is often associated with osteoarthritis (OA) and may even precede the onset of OA symptoms. Although targeting synovial inflammation has shown therapeutic promise in OA, synovium's heterogeneous composition, multiple cell types contributing to inflammatory response, indicates that focusing on a single population not provide most favorable results. This investigation employed scRNA-seq tissues from both human murine sources, revealing fibroblasts macrophages expressing high levels Podoplanin (PDPN). These cells constitute approximately 70% total display pro-inflammatory properties. Drawing inspiration unique interaction between PDPN CLEC-2, we engineered mesenchymal stromal cell-derived exosomes overexpress CLEC-2 (ExosomeCLEC-2) encapsulated liquiritigenin-loaded poly (lactic-co-glycolic acid) (PLGA) within ExosomeCLEC-2 membrane (EMCLEC-2), creating PDPN-targeting nanoparticle system called EMCLEC-2-PLGA-liquiritigenin (EMPL). Remarkably, EMPL concurrently targets PDPNhigh macrophages, exhibiting anti-inflammatory effects both vitro in vivo, preventing cartilage degeneration traumatic model. In summary, our research highlights potential developing platform can target mitigate processes offering novel promising strategy for treatment osteoarthritis.

Язык: Английский

Процитировано

0