Synergistic therapeutic antitumor effect of PD-1 blockade cellular vesicles in combination with Iguratimod and Rhodium nanoparticles

Younis, Muhammad Rizwan; Wu, Yongjian; Fang, Qiongyan; Shan, Hong; Huang, Xi

doi:10.1016/j.jcis.2023.06.030

Cited by 6 publications

(4 citation statements)

References 38 publications

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“…Since ROS are pivotal modulators in apoptosis ( 18 ), we next applied assays to determine if the elevated apoptosis of NSCLC cells was triggered by ROS production. We found that MBZ could induce ROS generation, which could be rescued by administration of NAC (10 mM), a ROS scavenger ( Figure 3C ).…”

Section: Resultsmentioning

confidence: 99%

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Liang,

Chen,

Pan

et al. 2024

J Thorac Dis

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Background The incidence and mortality of non-small cell lung cancer (NSCLC) are extremely high. Previous research has confirmed that the signal transducer and activator of the transcription 3 (STAT3) protein critically participate in the tumorigenesis of NSCLC. Mebendazole (MBZ) has exerts a larger number of pharmacological activities and has anticancer effects in lung cancer, but its mechanism of action remains unclear. This study thus aimed to clarify the impacts of MBZ on NSCLC cell. Methods Cell proliferation, migration, and apoptosis were investigated via cell counting kit 8 (CCK-8) assay, Transwell assay, colony formation assay, wound-healing assay, and flow cytometry. Reactive oxygen species (ROS) were detected with a multifunctional microplate reader. Markers of cell migration and apoptosis were detected with Western blotting. The transcriptional activity of STAT3 was detected via luciferase assay. ROS scavenger N-acetylcysteine (NAC) was used to determine the effect of MBZ on NSCLC via ROS-regulated STAT3 inactivation and apoptosis. A xenograft model was constructed in vivo to investigate the role of MBZ in NSCLC tumor growth. Results The findings demonstrated that MBZ inhibited NSCLC cell proliferation and migration while promoting apoptosis through triggering ROS generation. In addition, the Janus kinase 2 (JAK2)-STAT3 signaling pathway was abrogated with the treatment of MBZ. NAC could distinctly weaken MBZ-induced apoptosis and STAT3 inactivation. Moreover, MBZ inhibited the tumor growth of NSCLC in vivo . Conclusions In summary, MBZ inhibited NSCLC cell viability and migration by inducing cell apoptosis via the ROS-JAK2-STAT3 signaling pathway. These data provide a theoretical basis for the use of MBZ in treating NSCLC.

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Section: Resultsmentioning

confidence: 99%

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Liang,

Chen,

Pan

et al. 2024

J Thorac Dis

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“…Previously, PLGA MPs/NPs have been fabricated with varying sizes and morphologies for co-coupling on the surface, as well as for encapsulation of drugs inside the MPs/NPs. This allows controlled and sustained delivery of drugs and other molecules such as RNAs, antibodies, and cytokines to specific organs without causing any organ toxicity issues ( 26 , 57 , 58 ). Recently, a novel platform was developed to encapsulate exosomes in PLGA MPs/SMPs, which enabled a prolonged release of these exosomes to modulate dentiogenesis ( 55 ) and periprosthetic osteolysis ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis

Shahzad,

Wang,

et al. 2024

Front. Immunol.

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IntroductionAllergic rhinitis (AR) is an upper airway inflammatory disease of the nasal mucosa. Conventional treatments such as symptomatic pharmacotherapy and allergen-specific immunotherapy have considerable limitations and drawbacks. As an emerging therapy with regenerative potential and immunomodulatory effect, mesenchymal stem cell-derived exosomes (MSC-Exos) have recently been trialed for the treatment of various inflammatory and autoimmune diseases.MethodsIn order to achieve sustained and protected release of MSC-Exos for intranasal administration, we fabricated Poly(lactic-co-glycolic acid) (PLGA) micro and nanoparticles-encapsulated MSC-Exos (PLGA-Exos) using mechanical double emulsion for local treatment of AR. Preclinical in vivo imaging, ELISA, qPCR, flow cytometry, immunohistochemical staining, and multiomics sequencing were used for phenotypic and mechanistic evaluation of the therapeutic effect of PLGA-Exos in vitro and in vivo.ResultsThe results showed that our PLGA platform could efficiently encapsulate and release the exosomes in a sustained manner. At protein level, PLGA-Exos treatment upregulated IL-2, IL-10 and IFN-γ, and downregulated IL-4, IL-17 and antigen-specific IgE in ovalbumin (OVA)-induced AR mice. At cellular level, exosomes treatment reduced Th2 cells, increased Tregs, and reestablished Th1/Th2 balance. At tissue level, PLGA-Exos significantly attenuated the infiltration of immune cells (e.g., eosinophils and goblet cells) in nasal mucosa. Finally, multiomics analysis discovered several signaling cascades, e.g., peroxisome proliferator-activated receptor (PPAR) pathway and glycolysis pathway, that might mechanistically support the immunomodulatory effect of PLGA-Exos.DiscussionFor the first time, we present a biomaterial-facilitated local delivery system for stem cell-derived exosomes as a novel and promising strategy for AR treatment.

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“…The Cell Counting Kit-8 (CCK-8) assay was used to determine cell viability as per reported method [14]. Briefly, TMZ-resistant glioma cells (U251-TMZ-R and U87-TMZ-R) were seeded in 96-well plates at a density of 1 × 10 3 cells/well overnight, and then treated with AMR-PLGA-NPs (6 µM) and TMZ (1 mM).…”

Section: Cell Viability Assaymentioning

confidence: 99%

Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma

Younis,

Shaikh,

Shahzad

et al. 2024

Biomed. Mater.

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Glioblastoma (GBM) is an aggressive and deadly brain tumor, and currently, there is no effective cure available for its treatment. Although nanotechnology-based strategies have shown great potential in treating GBM, a major concern is the lack of efficient clearance of these nanoparticles from the body's organs, which limits their translation from laboratory studies to clinical settings. To address this issue, a study was conducted to investigate the potential of using amrubicin (AMR) encapsulated in poly (lactic-co-glycolic acid) nanoparticles (AMR-PLGA-NPs) against temozolomide (TMZ) resistant GBM. The study found that AMR-PLGA-NPs significantly inhibited the cell viability and migration of TMZ-resistant GBM cells. Additionally, the nanoparticles were effective in suppressing the PI3K/AKT signaling pathway, inducing apoptosis in TMZ-resistant glioma cancer cells and glioma stem-like cells (GSCs) by activating PTEN. Furthermore, AMR-PLGA-NPs can pass the biological barrier in in vivo mice model. These findings indicate that AMR-PLGA-NPs can be an effective and flexible nanoplatform for treating GBM while addressing drug resistance issues. Overall, the study demonstrates the potential of AMR-PLGA-NPs as a stable and safe treatment option for GBM, addressing the major issue of drug resistance in these types of tumors.

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Synergistic therapeutic antitumor effect of PD-1 blockade cellular vesicles in combination with Iguratimod and Rhodium nanoparticles

Cited by 6 publications

References 38 publications

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Mebendazole induces apoptosis and inhibits migration via the reactive oxygen species-mediated STAT3 signaling downregulation in non-small cell lung cancer

Immunomodulatory effect of PLGA-encapsulated mesenchymal stem cells-derived exosomes for the treatment of allergic rhinitis

Amrubicin encapsulated PLGA NPs inhibits the PI3K/AKT signaling pathway by activating PTEN and inducing apoptosis in TMZ-resistant Glioma

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