scholarly journals Dual Enzyme-like Performances of PLGA Grafted Maghemite Nanocrystals and Their Synergistic Chemo/Chemodynamic Therapy for Human Lung Adenocarcinoma A549 Cells

2020 ◽  
Author(s):  
Xueqin Wang ◽  
Miao Cui ◽  
Fan Ouyang ◽  
Yuqi Guo ◽  
Ruifang Li ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Lung Tumor ◽  
Tumor Therapy ◽  
A549 Cells ◽  
Inorganic Nanoparticles ◽  
Poly Lactic Acid ◽  
Catalytically Active ◽  
Endogenous Peroxidase ◽  
Lung Adenocarcinoma A549 ◽  
The One

Abstract Advancing nanocatalytic therapies of tumors formed on non-toxic but catalytically active inorganic nanoparticles (NPs) have aroused great interest in tumor therapy recently, but the limited reactive oxygen species within tumors may limit treatment efficiency. Therefore, the combination of chemotherapy and chemodynamic therapy is a promising treatment strategy. Herein, poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles (NPPLGA) with dual response of endogenous peroxidase (POD)- and catalase (CAT)-like activities has been reported. On the one hand, the NPPLGA could serve as a drug delivery system for doxorubicin (DOX), an anti-tumor drug used to treat lung adenocarcinoma A549 cells. On the other hand, based on the mimetic enzyme properties of NPPLGA, it can be combined with DOX to treat lung cancer. The results show that the NPPLGA could be simulated the CAT-like activity to decompose hydrogen peroxide (H2O2) into H2O and O2 under neutral tumor microenvironment, so as to reduce the oxidative damage caused by H2O2 to lung adenocarcinoma A549 cells. Under acidic microenvironment, NPPLGA could simulate POD-like activity to effectively catalyze the decomposition of H2O2 to produce highly toxic hydroxyl radicals (•OH) to induce the death of tumor-cell through regular catalytic reaction of Fenton. Furthermore, the POD-like activity of NPPLGA synergistic with DOX can promote the apoptosis and destruction of A549 cells and enhance the antitumor impact of DOX-NPPLGA. Therefore, this study provides an efficacious dual inorganic biomimetic nanozyme-based nanoplatform for lung tumor treatment.

Dual Enzyme-Like Performances of PLGA Grafted Maghemite Nanocrystals and Their Synergistic Chemo/Chemodynamic Treatment for Human Lung Adenocarcinoma A549 Cells

2021 ◽  
Vol 17 (6) ◽  
pp. 1007-1019
Author(s):  
Miao Cui ◽  
Hui-Ru Zhang ◽  
Fan Ouyang ◽  
Yu-Qi Guo ◽  
Rui-Fang Li ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Lung Adenocarcinoma ◽  
Therapeutic Strategy ◽  
A549 Cells ◽  
Inorganic Nanoparticles ◽  
Poly Lactic Acid ◽  
Dual Response ◽  
Catalytically Active ◽  
Endogenous Peroxidase ◽  
Lung Adenocarcinoma A549

In recent years, the emergence of non-toxic but catalytically active inorganic nanoparticles has attracted great attention for cancer treatment, but the therapeutic effect has been affected by the limited reactive oxygen species in tumors. Therefore, the combination of chemotherapy and chemodynamic therapy is regarded as a promising therapeutic strategy. In this paper, we reported the preparation and bioactivity evaluation of poly(lactic acid-co-glycolic acid) (PLGA) grafted-γ-Fe2O3 nanoparticles with dual response of endogenous peroxidase and catalase like activities. Our hypothesis is that PLGAgrafted γ-Fe2O3 nanoparticles could be used as a drug delivery system for the anti-tumor drug doxorubicin to inhibit the growth of lung adenocarcinoma A549 cells; meanwhile, based on its mimic enzyme properties, this kind of nanoparticles could be combined with doxorubicin in the treatment of A549 cells. Our experimental results showed that the PLGAgrafted γ-Fe2O3 nanoparticles could simulate the activity of catalase and decompose hydrogen peroxide into H2O and oxygen in neutral tumor microenvironment, thus reducing the oxidative damage caused by hydrogenperoxide to lung adenocarcinoma A549 cells. In acidic microenvironment, PLGA grafted γ-Fe2O3 nanoparticles could simulate the activity of peroxidase and effectively catalyze the decomposition of hydrogen peroxide to generate highly toxic hydroxyl radicals, which could cause the death of A549 cells. Furthermore, the synergistic effect of peroxidase-like activity of PLGA-grafted γ-Fe2O3 nanoparticles and doxorubicin could accelerate the apoptosisand destruction of A549 cells, thus enhancing the antitumor effect of doxorubicin-loaded PLGA-grafted γ-Fe2O3 nanoparticles. Therefore, this study provides an effective nanoplatform based on dual inorganic biomimetic nanozymes for the treatment of lung cancer.

scholarly journals Radio-sensitization effect of an mTOR inhibitor, temsirolimus, on lung adenocarcinoma A549 cells under normoxic and hypoxic conditions

2015 ◽  
Vol 56 (4) ◽  
pp. 663-668 ◽  
Author(s):  
Hiroki Ushijima ◽  
Yoshiyuki Suzuki ◽  
Takahiro Oike ◽  
Mayumi Komachi ◽  
Yuya Yoshimoto ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Mtor Inhibitor ◽  
A549 Cells ◽  
Hypoxic Conditions ◽  
Lung Adenocarcinoma A549 ◽  
Sensitization Effect

scholarly journals Biological Evaluation of Alkyl Triphenylphosphonium Ostruthin Derivatives as Potential Anti-Inflammatory Agents Targeting the Nuclear Factor κB Signaling Pathway in Human Lung Adenocarcinoma A549 Cells

BioChem ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 107-121
Author(s):  
Nghia Trong Vo ◽  
Eiichi Kusagawa ◽  
Kaori Nakano ◽  
Chihiro Moriwaki ◽  
Yasunobu Miyake ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Human Lung Adenocarcinoma ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Lung Adenocarcinoma A549

Ostruthin (6-geranyl-7-hydroxycoumarin) is one of the constituents isolated from Paramignya trimera and has been classified as a simple coumarin. We recently reported the synthesis of alkyl triphenylphosphonium (TPP) derivatives from ostruthin and evaluated their anticancer activities. In the present study, we demonstrated that alkyl TPP ostruthin derivatives inhibited the up-regulation of cell-surface intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells stimulated with tumor necrosis factor-α (TNF-α) without affecting cell viability, while ostruthin itself exerted cytotoxicity against A549 cells. The heptyl TPP ostruthin derivative (termed OS8) attenuated the up-regulation of ICAM-1 mRNA expression at concentrations higher than 40 µM in TNF-α-stimulated A549 cells. OS8 inhibited TNF-α-induced nuclear factor κB (NF-κB)-responsive luciferase reporter activity at concentrations higher than 40 µM, but did not affect the translocation of the NF-κB subunit RelA in response to the TNF-α stimulation at concentrations up to 100 µM. A chromatin immunoprecipitation assay showed that OS8 at 100 µM prevented the binding of RelA to the ICAM-1 promoter. We also showed that OS8 at 100 µM inhibited the TNF-α-induced phosphorylation of RelA at Ser 536. Moreover, the TNF-α-induced phosphorylation of an inhibitor of NF-κB α and extracellular signal-regulated kinase was reduced by OS8. These results indicate that OS8 has potential as an anti-inflammatory agent that targets the NF-κB signaling pathway.

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