3 resultados para Kung-fu
em Deakin Research Online - Australia
Resumo:
Hollow mesoporous silica nanoparticles were successfully fabricated and functionalized with appropriate silanes. After modifications, amine, carboxyl, cyano, and methyl groups were grafted onto the nanoparticles and all functionalized hollow mesoporous silica nanoparticles maintained a spherical and hollow structure with a mean diameter of ~120 nm and a shell thickness of ~10 nm. The loading capacity of the hollow mesoporous silica nanoaprticles to the anticancer drug, 5-fluorouracil, can be controlled via precise functionalization. The presence of amine groups on the surface of nanoparticles resulted in the highest loading capacity of 28.89%, due to the amine functionalized nanoparticles having a similar hydrophilicity but reverse charge to the drug. In addition, the change in pH leads to the variation of the intensity of electrostatic force between nanoparticles and the drug, which finally affects the loading capacity of amine functionalized hollow mesoporous silica nanoparticles to some extent. Higher drug loading was observed at pH of 7.4 and 8.5 as 5-fluorouracil becomes more deprotonated in alkaline conditions. The improved drug loading capacity by amine functionalized hollow mesoporous silica nanoparticles has demonstrated that they can become potential intracellular 5-fluorouracil delivery vehicles for cancers.
Resumo:
Acquired drug resistance (ADR) can be developed in colorectal cancer cells after 5-fluorouracil (5-FU) treatment and diminish the effectiveness of chemotherapy. In this work, acquired 5-FU resistance in the colorectal cancer cell line SW480 was obtained with the up-regulation of dihydropyrimidine dehydrogenase (DPYD) gene expression which can convert 5-FU to its inactive metabolite. To overcome ADR in colorectal cancer, hollow mesoporous silica nanoparticles (HMSNs) grafted with epidermal growth factor (EGF) were used as nanocarriers to deliver 5-FU to colorectal cancer cells with acquired drug resistance. The effect and mechanism of 5-FU loaded EGF grafted HMSNs (EGF-HMSNs-5-FU) in overcoming acquired drug resistance in SW480/ADR cells were studied. The EGF-HMSNs were demonstrated to be specifically internalized in EGFR overexpressed SW480/ADR cells via a receptor-mediated endocytosis and can escape from endo-lysosomes. The EGF-HMSNs-5-FU exhibited much higher cytotoxicity on SW480/ADR cells than HMSNs-5-FU and free 5-FU while the plain HMSNs did not show significant cytotoxicity. The mechanism of EGF-HMSNs-5-FU in overcoming drug resistance in SW480/ADR cells could be attributed to the specific internalization of EGF-HMSNs-5-FU in EGFR overexpressed cells which can lead to high intracellular drug accumulation and cause cell death through S phase arrest.