| Summary: | There have been many studies on improving the efficacy of cisplatin and on identifying safe compounds that can overcome multi-drug resistance (MDR) acquired by cancer cells. Our previous research showed that polyethylene glycol-modified titanium dioxide nanoparticles (TiO<sub>2</sub> PEG NPs) affect cell membrane receptors, resulting in their aggregation, altered localization and downregulation. TiO<sub>2</sub> PEG NPs may affect P-glycoprotein (P-gp), a membrane efflux channel involved in MDR. In this study, we investigated the effect of TiO<sub>2</sub> PEG NPs on cisplatin cytotoxicity. We used HepG2 cells, which highly express P-gp and A431 cells, which show low expression of P-gp. The results showed that 10 µg/mL 100 nm TiO<sub>2</sub> PEG NPs increased intracellular cisplatin levels and cytotoxicity in HepG2 cells but not in A431 cells. TiO<sub>2</sub> PEG NPs treatment decreased the expression level of P-gp in HepG2 cells. Our findings indicate that TiO<sub>2</sub> PEG NPs enhance cisplatin cytotoxicity by down regulating P-gp and that TiO<sub>2</sub> PEG NPs are promising candidates for inhibiting P-gp and reversing drug resistance acquired by cancer cells.
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