Chitosan nanoparticles triggered the induction of ROS-mediated cytoprotective autophagy in cancer cells

Wang, Hao; Yu, Xiwei; Su, Chang; Shi, Yijie; Zhao, Liang

doi:10.1080/21691401.2017.1423494

Cited by 51 publications

(27 citation statements)

References 27 publications

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“…The molecular mechanism underlying autophagy has been extensively investigated in recent years. The mitochondrial antioxidant Mito-TEMPO (mitochondrial-targeted SOD mimetic) enhanced SOD2 activity but not SOD2 levels, significantly suppressed the 5-ALA-PDT-mediated increase in autophagy level, and consistent with many studies revealed that ROS can induce autophagy [34] , [35] , [36] .…”

Section: Discussionsupporting

confidence: 82%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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Keloids exhibit cancer-like properties without spontaneous regression and usually recur post excision. Although photodynamic therapy (PDT) is a promising treatment, details of the mechanisms remain to be elucidated. In this study, we investigated mechanisms involved in 5-Aminolevulinic Acid (5-ALA)–based PDT against keloid. Found that 5-ALA-PDT induced superoxide anion-dependent autophagic cell death. Application of autophagy inhibitor 3-Methyladenine (3-MA) significantly prevented the effect that 5-ALA-PDT induced keloid–derived fibroblasts death, but Z-VAK-FMK (apoptotic inhibitor) did not. Interestingly, 5-ALA-PDT promoted the SIRT3 protein expression and the activity of mitochondrial superoxide dismutase 2 (SOD2), but SIRT1 protein expression level was decreased. SOD2 as a key enzyme can decrease mitochondrial ROS (mROS) level, Deacetylation of SOD2 by SIRT3 regulates SOD2 enzymatic activity has been identified. Then we explored SOD2 acetylation level with immunoprecipitation, found that 5-ALA-PDT significantly increased the acetylation levels of SOD2. In order to confirm deacetylation of SOD2 regulated by SIRT3, 3-TYP (SIRT3 inhibitor) was used. Found that inhibition of SIRT3 by 3-TYP significantly increased the level of SOD2 acetylation level compared with control group or 5-ALA-PDT group. To explore the connection of SIRT1 and SIRT3, cells were treated with EX527(SIRT1 inhibitor) or SRT1720 (SIRT1 activator), and EX527 increased SIRT3 protein level, however, SRT1720 displayed the opposite effect in the present or absence of 5-ALA-PDT. Moreover SIRT1-inhibited cells are more resistant to 5-ALA-PDT and showing decreased ROS accumulation. These results may demonstrate that 5-ALA-PDT induced SIRT1 protein level decreased, which promoted the effect of SIRT3 increased activity of SOD2 that can reduce mROS level, and then compromised 5-ALA-PDT induced autophagic cell death.

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Section: Discussionsupporting

confidence: 82%

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Liu

Ouyang

et al. 2019

Redox Biology

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“…Literature review showed several contradictory results regarding Chit NPs effect on cellular ROS production. One study suggested that Chit NPs had an inhibitory activity (Bor et al, 2016), two studies reported no Chit NPs effect (Omar Zaki et al, 2015;Arora et al, 2016) and three reported a stimulating effect (Hu et al, 2011;Sarangapani et al, 2018;Wang et al, 2018) on basal ROS cellular production. Concerning the polymer, same conflicting results were also found (Arora et al, 2016;Salehi et al, 2017;Sarangapani et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

Jesus

Marques

Duarte

et al. 2020

Front. Bioeng. Biotechnol.

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Nanoparticles (NPs) assumed an important role in the area of drug delivery. Despite the number of studies including NPs are growing over the last years, their side effects on the immune system are often ignored or omitted. One of the most studied polymers in the nano based drug delivery system field is chitosan (Chit). In the scientific literature, although the physicochemical properties [molecular weight (MW) or deacetylation degree (DDA)] of the chitosan, endotoxin contamination and appropriate testing controls are rarely reported, they can strongly influence immunotoxicity results. The present work aimed to study the immunotoxicity of NPs produced with different DDA and MW Chit polymers and to benchmark it against the polymer itself. Chit NPs were prepared based on the ionic gelation of Chit with sodium tripolyphosphate (TPP). This method allowed the production of two different NPs: Chit 80% NPs (80% DDA) and Chit 93% NPs (93% DDA). In general, we found greater reduction in cell viability induced by Chit NPs than the respective Chit polymers when tested in vitro using human peripheral blood monocytes (PBMCs) or RAW 264.7 cell line. In addition, Chit 80% NPs were more cytotoxic for PBMCs, increased reactive oxygen species (ROS) production (above 156 µg/mL) in the RAW 264.7 cell line and interfered with the intrinsic pathway of coagulation (at 1 mg/mL) when compared to Chit 93% NPs. On the other hand, only Chit 93% NPs induced platelet aggregation (at 2 mg/mL). Although Chit NPs and Chit polymers did not stimulate the nitric oxide (NO) production in RAW 264.7 cells, they induced a decrease in lipopolysaccharide (LPS)-induced NO production at all tested concentrations. None of Chit NPs and polymers caused hemolysis, nor induced PBMCs to secrete TNF-α and IL-6 cytokines. From the obtained results we concluded that the DDA of the Chit polymer and the size of Chit NPs influence the in vitro immunotoxicity results. As the NPs are more cytotoxic than the corresponding polymers, one should be careful in the extrapolation of trends from the polymer to the NPs, and in the comparisons among delivery systems prepared with different DDA chitosans.

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“…ROS plays an complicated role in cancer process, it can not only mediated cancer cytoprotective autophagy [35] but also directly induce apoptosis. Additionally, we also found that the combination of DOX and Se@SiO 2 could augment the antitumour efficacy of DOX.…”

Section: Discussionmentioning

confidence: 99%

Se@SiO₂ nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage

Deng

Chen

Zhang

et al. 2018

Artificial Cells, Nanomedicine, and Biotechnology

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Doxorubicin (DOX) is an effective anticancer drug which is widely used in clinical treatment. However, the severe cardiotoxicity limits its use. Thus, it is an urgent need to attenuate the toxicity of DOX without impairing its efficacy. Many studies show that Se may protect normal tissues from damages of some anticancer drugs. Recently, Se@SiO nanocomposites emerges as better substitutes for direct element Se in treatment of cancer cells for their ideal biocompatibility. In the present article, we synthesized Se@SiO nanocomposites and confirmed their characterization according to previous studies. We accomplished a conjunctive use of Se@SiO nanocomposites with DOX then explored the toxicity and efficacy of this combination. In the in vivo experiments, the survival rate of mice with DOX treatment was significantly increased by Se@SiO. And Se@SiO has few interference to the therapeutic effect of DOX. Particularly, Se@SiO significantly attenuated DOX-induced myocardial tissue damage (serum index, apoptosis index, western-blot index) and protected mice from reduction in LVEF induced by DOX in mice model. In summary, we concluded that the protective effect of Se@SiO in DOX-induced cardiotoxicity was possibly attributable to the inhibition of ROS production, showing great potential of Se@SiO nanocomposite in the clinical use of DOX.

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Chitosan nanoparticles triggered the induction of ROS-mediated cytoprotective autophagy in cancer cells

Cited by 51 publications

References 27 publications

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

Se@SiO₂ nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage

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Chitosan nanoparticles triggered the induction of ROS-mediated cytoprotective autophagy in cancer cells

Cited by 51 publications

References 27 publications

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Efficacy of 5-aminolevulinic acid–based photodynamic therapy against keloid compromised by downregulation of SIRT1-SIRT3-SOD2-mROS dependent autophagy pathway

Chitosan Nanoparticles: Shedding Light on Immunotoxicity and Hemocompatibility

Se@SiO2 nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage

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Product

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Se@SiO₂ nanocomposites attenuate doxorubicin-induced cardiotoxicity through combatting oxidative damage