The nano-based theranostics for respiratory complications of COVID-19

Ghasemzad, Mahsa; Hashemian, Seyed Mohammad Reza; Memarnejadian, Arash; Akbarzadeh, Iman; Vosough, Massoud

doi:10.1080/03639045.2021.1994989

Cited by 4 publications

(2 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…10 Recently, positively charged cationic liposomes have emerged as preferred siRNA carriers due to their high loading capacity and significantly enhanced cellular internalization through adsorptive interactions with the cell membrane. 11 Furthermore, in our previous studies, 12,13 siRNA encapsulated in cationic liposomes shows preferential uptake by macrophages and fibroblasts following intratracheal administration. Therefore, siRNA therapy based on cationic liposomes may represent an optimal strategy for disrupting macrophage-fibroblast crosstalk.…”

Section: Introductionmentioning

confidence: 88%

Localized Administration of Bcar3 siRNA via Nano-Self-Assembly to Treat Idiopathic Pulmonary Fibrosis by Disrupting Macrophage-Fibroblast Crosstalk

Zeng,

Wang,

Liu

et al. 2024

IJN

View full text Add to dashboard Cite

Background Idiopathic pulmonary fibrosis (IPF) is a severe interstitial lung disease characterized by chronic lung injury leading to macrophage infiltration and fibroblast activation. However, there is no effective therapeutic strategy targeting the crucial crosstalk between macrophages and fibroblasts to halt IPF progression. Methods Studies were conducted in IPF patients and fibrotic mice models to elucidate the role of Bcar3 in the pathogenesis of pulmonary fibrosis. The effect of Bcar3 on macrophage polarization, fibroblast activation, and related signaling pathways were next investigated to unravel the underlying mechanisms. Results Our study elucidates a marked increase in Bcar3 expression in lung tissues from IPF patients and fibrotic mice, recording 1.7 and 7.8-fold increases compared to control subjects, respectively. Additionally, Bcar3 was found to significantly enhance macrophage activation and fibroblast differentiation, observable in both in vivo and in vitro settings. Mechanistically, the upregulation of Bcar3 in macrophages was reliant on Stat6, while in fibroblasts, it depended on TGFβR1/Smad3. Furthermore, Bcar3 augmented IL-4/Stat6 pathway in macrophages and TGF-β/Smad3 pathway in fibroblasts, supporting a synergistic activation loop that expedited lung fibrogenesis. Notably, intratracheal injection of liposomes containing Bcar3 siRNA precisely delivered gene therapeutics to lung macrophages and fibroblasts, effectively reducing Bcar3 expression to 59% of baseline levels. Importantly, this intervention protected mice from lung fibrosis induced by either FITC or bleomycin, as well as human precision-cut lung slices against TGF-β1 stimulation. Conclusion Our study underscores the pivotal role of Bcar3 in orchestrating the macrophage-fibroblast crosstalk during pulmonary fibrosis progression. Targeting Bcar3 emerges as a novel therapeutic avenue to halt IPF progression and enhance patient prognosis.

show abstract

Section: Introductionmentioning

confidence: 88%

Localized Administration of Bcar3 siRNA via Nano-Self-Assembly to Treat Idiopathic Pulmonary Fibrosis by Disrupting Macrophage-Fibroblast Crosstalk

Zeng,

Wang,

Liu

et al. 2024

IJN

View full text Add to dashboard Cite

show abstract

“…Vaccination has significantly reduced COVID-19 mortality rates; however, the best treatment approach is still being debated [ 20 ]. New treatment strategies, such as nanomedicine-based approach, cell-based therapy, and adoptive immunotherapy have emerged to treat COVID-19 patients [ 21 – 23 ]. Among these, cell-based therapies using mesenchymal stem cells (MSCs), have shown promising results in pilot studies and also in clinical trials [ 24 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

Allogenic mesenchymal stromal cells and their extracellular vesicles in COVID-19 induced ARDS: a randomized controlled trial

et al. 2023

Self Cite

View full text Add to dashboard Cite

Background and aims The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients. Materials and methods COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention. Results A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041). Conclusion MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events. Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073.

show abstract