The Effects of TiO2 Nanoparticles on Cisplatin Cytotoxicity in Cancer Cell Lines

Abstract

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 (TiO2 PEG NPs) affect cell membrane receptors, resulting in their aggregation, altered localization and downregulation. TiO2 PEG NPs may affect P-glycoprotein (P-gp), a membrane efflux channel involved in MDR. In this study, we investigated the effect of TiO2 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 TiO2 PEG NPs increased intracellular cisplatin levels and cytotoxicity in HepG2 cells but not in A431 cells. TiO2 PEG NPs treatment decreased the expression level of P-gp in HepG2 cells. Our findings indicate that TiO2 PEG NPs enhance cisplatin cytotoxicity by down regulating P-gp and that TiO2 PEG NPs are promising candidates for inhibiting P-gp and reversing drug resistance acquired by cancer cells.

Mechanisms of Multidrug Resistance in Cancer Chemotherapy

“…Furthermore, the effect of novel P-gp inhibitors, polyethylene glycol-modified titanium dioxide nanoparticles (TiO 2 PEG NPs), on cisplatin cytotoxicity against P-gp overexpressing HepG2 cells was examined. This study showed that increased cisplatin cytotoxicity was associated with downregulation of the expression of P-gp in HepG2 cells by TiO 2 PEG NPs [35].…”

“…This includes ERCC1-XPF inhibitors (E-X PPI2, E-X AS7, compound 13, and compound B5), RPA inhibitors (TDRL-551, SMI MCI13E, and TDRL-55 derivatives), ATR kinase inhibitors (VX-970 and AZD6738), DNA-PKcs inhibitors (NU7026, NU7441, and AZD7648), HR inhibitors (B02 compound), and TLS inhibitors (JH-RE-06, T2AA, and compounds 4 and 5) [88,[91][92][93][94][95][98][99][100][101][102][103][104][105][106]. Other substances, such as taxifolin, sitravatinib, cinobufagin, crown ethers, ascorbic acid, TTM, so-PXA, mPEG glycine-quinidine conjugate, and TiO 2 PEG NPs that have been designed to block efflux of drugs outside the cancer cells are known as P-gp inhibitors [18,[28][29][30][31][32][33][34][35]. Another group involves drugs that are capable of increasing metabolism of xenobiotics in tumor cells.…”

Characterization of cisplatin-loaded chitosan nanoparticles and rituximab-linked surfaces as target-specific injectable nano-formulations for combating cancer

“…Oridonin-entrapped galactosylated chitosan nanoparticles (ORI-GC-NP) exhibited IC50 values of 31.07 and 26.59 µM against MCF-7 cells and HepG2.cells, respectively 45 . Furthermore, a study reported that IC50 values of polyethylene glycol-modified titanium dioxide nanoparticles (TiO2 PEG NPs) against HepG2 and A431 cells were 12.00 and 6.00 µg/mL, respectively 46 .…”

Preparation of dendritic carboranyl glycoconjugates as potential anticancer therapeutics

“…The IC 50 value of the most commonly used cancer drug, cisplatin has been reported to be between 6 mg mL À1 to 9 mg mL À1 (20 to 30 mM) for A431 skin cancer cells and 6 mg mL À1 (20 mM) for MCF-7 breast cancer cells. [45][46][47] It is more than two fold higher than the IC 50 values observed for carboranyl glycoconjugates 15 and 17 (with three glucose and galactose units with o-carborane). The IC 50 of cisplatin is more than three fold higher than the IC 50 values observed for carboranyl glycoconjugates 19 and 21 (with three glucose and galactose units with o-carborane).…”