90 K increased delivery efficiency of extracellular vesicles through mediating internalization

Zhu, Guiquan; Yang, Fan; Wei, Hongxuan; Meng, Wanrong; Gan, Jianguo; Wang, Linlin; He, Chuanshi; Lü, Shun; Cao, Bangrong; Luo, Huaichao; Han, Bo; Li, Ling

doi:10.1016/j.jconrel.2022.12.034

Cited by 3 publications

(4 citation statements)

References 35 publications

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“…It is believed that the primary function of the EVs is to participate in cell-to-cell communication [38][39][40]. The internalization of the EVs into the cells is thought to be essential in this process [11][12][13]. Thus, we investigated whether PDE-EVs can penetrate into the P-MCs (Figure 3).…”

Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes

Szebeni,

Veres-Székely,

Pap

et al. 2024

Cells

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Among patients on peritoneal dialysis (PD), 50–80% will develop peritoneal fibrosis, and 0.5–4.4% will develop life-threatening encapsulating peritoneal sclerosis (EPS). Here, we investigated the role of extracellular vesicles (EVs) on the TGF-β- and PDGF-B-driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory PD. The impact of PDE-EVs on the epithelial–mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro and in vivo in the chlorhexidine digluconate (CG)-induced mice model of peritoneal fibrosis. PDE-EVs showed spherical morphology in the 100 nm size range, and their spectral features, CD63, and annexin positivity were characteristic of EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE- or PDGF-B-induced proliferation. Furthermore, PDE-EVs inhibited the PDE- or TGF-β-induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased the submesothelial thickening of CG-treated mice. We demonstrated that PDE-EVs significantly inhibit the PDGF-B- or TGF-β-induced fibrotic processes in vitro and in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.

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Section: Discussionmentioning

confidence: 99%

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes

Szebeni,

Veres-Székely,

Pap

et al. 2024

Cells

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show abstract

“…It is believed that the primary function of the EVs is to participate in the cell-to-cell communication [41][42][43]. Internalization of the EVs into the cells is thought to be essential in this process [11][12][13]. Thus, we investigated whether PDE-EVs can penetrate into the P-MCs (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Extracellular vesicles (EVs) are lipid bilayer-coated nanoparticles of biological origin released by different cell types [9,10]. The key function of EVs is related to the transfer of their molecular cargo into the neighbouring cells, which is suggested to modify the biological processes of the recipient cells [10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles of patients on peritoneal dialysis inhibit the TGF-β and PDGF-B mediated fibrotic processes

Szebeni,

Veres-Székely,

Pap

et al. 2024

Preprint

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Background: Peritoneal fibrosis develops in 50%-80%, and life-threatening encapsulating peritoneal sclerosis (EPS) in 0.5-4.4% of the patients on peritoneal dialysis (PD). Here we investigated the role of extracellular vesicles (EVs) on the transforming growth factor (TGF)-β and platelet derived growth factor (PDGF)-B driven processes of peritoneal fibrosis. EVs were isolated from the peritoneal dialysis effluent (PDE) of children receiving continuous ambulatory peritoneal dialysis (PD). The impact of PDE-EVs on the epithelial-mesenchymal transition (EMT) and collagen production of the peritoneal mesothelial cells and fibroblasts were investigated in vitro, and in vivo in the chlorhexidine digluconate (CG) induced mice model of peritoneal fibrosis. Results: PDE-EVs showed spherical morphology in the 100 nm size range, their spectral features, CD63, and annexin positivity was characteristic to EVs. PDE-EVs penetrated into the peritoneal mesothelial cells and fibroblasts and reduced their PDE or PDGF-B induced proliferation. Furthermore, PDE-EVs inhibited the PDE or TGF-β induced EMT and collagen production of the investigated cell types. PDE-EVs contributed to the mesothelial layer integrity and decreased submesothelial thickening of CG-treated mice. Conclusions: We demonstrated that PDE-EVs significantly inhibit the PDGF-B or TGF-β induced fibrotic processes in vitroand in vivo, suggesting that EVs may contribute to new therapeutic strategies to treat peritoneal fibrosis and other fibroproliferative diseases.

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“…LGALS3BP is involved in immunity, angiogenesis, cellular adhesion and migration and tumour microenvironment (TME) crosstalk, influencing tumour growth and progression (Capone et al, 2021). Recently, LGALS3BP has been indicated as one of the most abundant glycoproteins on the surface of extracellular vesicles (EVs) derived from ovarian cancer, endometrial cancer, pancreatic ductal adenocarcinoma, glioblastoma and neuroblastoma (Capone et al, 2020;Castillo et al, 2018;Dufrusine et al, 2023;Escrevente et al, 2013;Nakata et al, 2017;Song et al, 2021) and implicated in cargo delivery of these vesicles (Zhu et al, 2023), proposing a functional specialization for vesicular LGALS3BP. Interestingly, LGALS3BP was previously shown to affect cell growth and motility of OSCC cells by likely acting as an oncogene (Endo et al, 2013;Weng et al, 2008;Zhang et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

LGALS3BP is a potential target of antibody‐drug conjugates in oral squamous cell carcinoma

Cela,

Caponio,

Capone

et al. 2023

Oral Diseases

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ObjectiveThe aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody‐drug conjugate (ADC) therapy.MethodsFree and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT‐PCR, Western Blot analysis, and ELISA.ResultsLGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer‐derived extracellular vesicles. Moreover, LGALS3BP high‐expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC‐payload DM4, with an IC50 around 0.3 nM.ConclusionsThe present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC‐based therapy.

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90 K increased delivery efficiency of extracellular vesicles through mediating internalization

Cited by 3 publications

References 35 publications

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes

Extracellular Vesicles of Patients on Peritoneal Dialysis Inhibit the TGF-β- and PDGF-B-Mediated Fibrotic Processes

Extracellular vesicles of patients on peritoneal dialysis inhibit the TGF-β and PDGF-B mediated fibrotic processes

LGALS3BP is a potential target of antibody‐drug conjugates in oral squamous cell carcinoma

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