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Gemcitabine Nanoparticles Targeting Pancreatic Cancer Drug Delivery Systems In Vitro Evaluation

Posted on:2017-10-27Degree:MasterType:Thesis
Country:ChinaCandidate:K YanFull Text:PDF
GTID:2334330491459889Subject:Surgery
Abstract/Summary:PDF Full Text Request
Objective:Demonstrated the release of gemcitabine nanoparticles GEM-CHI-PEG in vitro, to detect the proliferation, apoptosis and expression of apoptosis associated genes in pancreatic cancer cells and normal cells.Method:Get the "Gemcitabine concentration-Absorbance" linear; Dynamic dialysis Determination the pH-sensitive release characteristics of nanoparticles. Confocal microscopy observed intracellular nanoparticles uptake experiments; Annexin V-FITC /PI double staining used to apoptosis experiments; CCK-8 assay determined the inhibition of nanoparticles in vitro; Real-time PCR detected the RNA expression level of Bel-2?Survivin and Bax gene.Result:Get the "Gemcitabine concentration-Absorbance" linear; Determined the pH-sensitive release characteristics of nanoparticles; The fluorescence intensity of nanoparticles intracellular were obvious; The apoptosis rates of GEM and GEM-CHI-PEG group increased significantly (p<0.05); The apoptosis rates of GEM-CHI-PEG group in Colo357 cells were significantly higher than HPDE (p<0.05); GEM group and GEM-CHI-PEG groups could significantly inhibit the growth of pancreatic cancer cells, and showed significant dose-dependent;When the drug concentration higher than 1?g/ml, the inhibition rates of GEM-CHI-PEG were higherthan GEM group (p<0.05). The Bcl-2 and Survivin expression was significantly decreased in GEM group and GEM-CHI-PEG group;the expression of pro-apoptotic genes Bax was significantly increased in GEM group and GEM-CHI-PEG group (p<0.05).Conclusion:GEM-CHI-PEG nanoparticles had pH-dependent release properties, and CHI-PEG nanoparticles showed good uptake of the cells and little toxicity; GEM-CHI-PEG can inhibit tumor cell growth, the toxicity in normal pancreatic ductal cells was lower than gemcitabine. GEM-CHI-PEG can inhibit apoptosis by inhibiting the expression of antiapoptotic genes and increasing the expression of pro-apoptotic genes;...
Keywords/Search Tags:Gemcitabine, Nanoparticles, Targeted therapy, pH-dependent release
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