الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
In this work we investigated the interaction between TiO2-PEG NPs and cancer cell lines. Then we investigated the ability of TiO2-PEG NPs to decrease MDR via inhibition of P-gp. After that we constructed EGF- targeted TiO2-PEG NPs and we proved that our newly constructed NPs could be more efficient and safer for cancer therapy and bioimaging. Our data showed that TiO2-PEG NPs increased cisplatin cytotoxicity and intracellular cisplatin uptake for P-gp expressing cell line, HepG2 cell line. And the possible mechanism of action for this effect could be the inhibition of P-gp function by TiO2-PEG NPs. These results suggest that TiO2 PEG NPs are promising candidates for reversing MDR and inhibiting P-gp functions in P-gp expressing cancer cell lines such as HepG2 cell line. Being safe and effective in low concentrations, would be an important advantage that could promote TiO2 PEG NPs for clinical trials. In case of A431 cells, that express low level of P-gp, TiO2 PEG NPs showed undesired effect, cisplatin cytotoxicity decreased due to the cell proliferation effect of TiO2 PEG NPs. Moreover, the cell proliferation effect of TiO2 PEG NPs would increase the risk of tumour overgrowth while being used for cancer bioimaging and cancer therapy. Therefore, our next step was to modify the surface of TiO2 PEG NPs by specific ligand in order to target specific receptor on certain cell lines. We constructed EGF-ligated TiO2 PEG NPs aiming to improving the therapeutic outcomes of TiO2 PEG NPs and decrease the risk of tumour overgrowth. Our results indicated that EGF conjugation increased the cellular uptake of TiO2 PEG NPs with decrease in its proliferative effect for A431 cells. Moreover, the data revealed that EGF-TiO2 PEG NPs increased cisplatin cytotoxicity for EGFRs expressing cancer cell line such as A431 cell line. These results suggested that EGF-TiO2-PEG NPs could increase the efficacy of TiO2 PEG NPs in cancer bioimaging and therapy such as PDD, PDT and PTT with decreased risk of cancer over-growth. Besides, EGF-TiO2 PEG NPs could increase cisplatin cytotoxicity for EGFRs expressing cancers and subsequently decrease the needed dose and reduce its side effects.