scholarly journals Glucose and Transferrin Liganded PLGA Nanoparticles Internalization in Non-Small Lung Cancer Cells

Author(s):  
Sarra Benammar ◽  
Fatima Mraiche ◽  
Jensa Mariam Joseph ◽  
Katerina Gorachinova

Introduction: Recently, after a decade of confusing results, several studies pointed out that overexpression of GLUT1 (glucose transporter 1) is a biomarker of worse prognosis in NSCLC. Nonetheless, the presence of transferrin (Tf receptor), which is overexpressed in most cancer tissues and most lung cancers as well, in NSCLC is also an indicator of very poor prognosis. Therefore, these ligands can be used for active targeting of lung cancer cells and improved efficacy of internalization of cancer therapy using nanomedicines. Objectives: Having the background, the main goal of the project was the assessment of the influence of the glucose and transferrin ligands on the efficacy of internalization of the designed (i) glucose decorated PLGA (poly lactic-coglycolic acid) nanoparticles (Glu-PLGA NPs) and (ii) transferrin decorated PLGA nanoparticles (Tf-PLGA NPs) in comparison to (iii) non-liganded PLGA NPs using a A549 lung cancer cells. Methods: Glu-PLGA NPs, Tf-PLGA NPs and PLGA NP - fluorescently labelled), were designed using a sonication assisted nanoprecipitation method. Further, physicochemical properties characterization (particle size analysis, zeta potential, FTIR analysis, DSC analysis), cytotoxicity evaluation using MTT test, and cell internalization studies of DTAF labelled NPs using fluorimetry in A549 NSCLC cell line were performed. Results: The results pointed to a significantly improved internalization rate of the liganded compared to PLGA NPs. Glu-PLGA NPs showed higher internalization rate compared to Tf-PLGA and PLGA NPs, in the serum-supplemented and serumfree medium even at normal levels of glucose in the cell growth medium. Conclusion: The developed nanocarriers offer unique advantages of enhanced targetability, improved cell internalization and decreased toxicity, which makes them promising solution for current therapeutic limitations.

ChemMedChem ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. 1892-1900 ◽  
Author(s):  
Carlotta Granchi ◽  
Yanrong Qian ◽  
Hyang Yeon Lee ◽  
Ilaria Paterni ◽  
Carolina Pasero ◽  
...  

2014 ◽  
Vol 88 (2) ◽  
pp. 529-538 ◽  
Author(s):  
Chuda Chittasupho ◽  
Kriengsak Lirdprapamongkol ◽  
Prartana Kewsuwan ◽  
Narong Sarisuta

Tumor Biology ◽  
2017 ◽  
Vol 39 (5) ◽  
pp. 101042831770621 ◽  
Author(s):  
Xiaojian Zhao ◽  
Caiping Lu ◽  
Weiwei Chu ◽  
Bing Zhang ◽  
Qiang Zhen ◽  
...  

Non–small cell lung cancer accounts for 85% of all types of lung cancer and is the leading cause of worldwide cancer-associated mortalities. MiR-124 is epigenetically silenced in various types of cancer and plays important roles in tumor development and progression. MiR-124 was also significantly downregulated in non–small cell lung cancer patients. Glycolysis has been considered as a feature of cancer cells; hypoxia-inducible factor 1-alpha/beta and Akt are key enzymes in the regulation of glycolysis and energy metabolism in cancer cells. However, the role of miR-124 in non–small cell lung cancer cell proliferation, glycolysis, and energy metabolism remains unknown. In this research, cell proliferation was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; furthermore, glucose consumption and lactic acid production were assessed; adenosine triphosphate content and NAD+/NADH were also detected. These tests were conducted using the normal non–small cell lung cancer cell line A549, which was transfected variedly with miR-mimics, miR-124 mimics, miR-124 inhibitor, pc-DNA3.1(+)-AKT1, and pc-DNA3.1(+)-AKT2 plasmid. Here, we show that miR-124 overexpression directly decreased cell growth, glucose consumption, lactate production, and energy metabolism. MiR-124 also negatively regulates glycolysis rate–limiting enzymes, glucose transporter 1 and hexokinase II. Our results also showed that miR-124 negatively regulates AKT1 and AKT2 but no regulatory effect on hypoxia-inducible factor 1-alpha/beta. Overexpression of AKT reverses the inhibitory effect of miR-124 on cell proliferation and glycolytic metabolism in non–small cell lung cancer. AKT inhibition blocks miR-124 silencing–induced AKT1/2, glucose transporter 1, hexokinase II activation, cell proliferation, and glycolytic or energy metabolism changes. In summary, this study demonstrated that miR-124 is able to inhibit proliferation, glycolysis, and energy metabolism, potentially by targeting AKT1/2–glucose transporter 1/hexokinase II in non–small cell lung cancer cells.


3 Biotech ◽  
2020 ◽  
Vol 10 (3) ◽  
Author(s):  
Mohammad Y. Alfaifi ◽  
Ali A. Shati ◽  
Serag Eldin I. Elbehairi ◽  
Usama A. Fahmy ◽  
Nabil A. Alhakamy ◽  
...  

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Xiaojin Wu ◽  
Weitao Wang ◽  
Yuanyuan Chen ◽  
Xiangqun Liu ◽  
Jindong Wang ◽  
...  

Lung cancer has very high mortality and glycyrrhizin was found to significantly inhibit the growth of lung cancer cells in vitro and tissues in mice. However, the detailed inhibitory role of glycyrrhizin in the growth of lung cancer is still unclear. In this study, we first found that glycyrrhizin inhibited the growth of lung tumor in PDX mice. And high level of HMGB1 promoted the migration and invasion of lung cancer cells, which was suppressed by glycyrrhizin. Moreover, glycyrrhizin reduced the activity of JAK/STAT signaling pathway, which is the upstream regulator of HMGB1. Therefore, this study revealed a potential mechanism by which glycyrrhizin can inhibit the progression of lung cancer.


Sign in / Sign up

Export Citation Format

Share Document