TiO2 eradicating cancer cells

.........Interestingly, the photocatalytic properties of TiO2-mediated toxicity have been shown to eradicate cancer cells.[16] and [17] It is now well established that TiO2 particles, on exposure to ultraviolet (UV) light, produce electrons and holes leading subsequently to the formation of ROS such as hydrogen peroxide, hydroxyl radicals, and superoxides.18 These oxygen species are highly reactive with cell membranes and the cell interior, with damaged areas depending on particle location upon excitation. Such oxidative reactions affect cell rigidity and chemical arrangement of surface structures, leading to cell toxicity.19 Despite promising outcomes in killing cancer cells, such treatments would be difficult to implement in clinical settings for the following reasons. First, UV light cannot penetrate deeply into human tissues, thus limiting this technique to superficial tumors.20 Second, UV-mediated production of ROS has a very short life span and thus would not be able to provide a continuous prolonged cancer-killing effect.19

Surface functionality has been shown to affect cell-particle interactions. Although it has been suggested that surface functionality should be the determining factor concerning cell uptake and subsequent activity inside the cell, studies that have varied surface functionality to investigate membrane binding, uptake, and internalization of nanoparticles are limited. We thus hypothesize that, by varying surface functionality, the cell toxicity of TiO2 particles can be altered. Three functional groups with various surface charges (-OH, -NH2, and –COOH) were included in this investigation. We found the effect of particle surface functionality on cell toxicity to be cell-dependent. 3T3 fibroblasts and B16F10 melanoma cells showed no significant response to functionalized or untreated particles at concentrations as high as 1 mg/mL.

These findings are in agreement with recent findings that TiO2 nanoparticle surface functionality (hydrophilic vs. hydrophobic) had insignificant effects on cell toxicity in an intratracheal rat model. These differences may be due to protein composition of the cell membrane and the manner in which these proteins interact with the TiO2 particles. In the case of the melanoma and 3T3 cells, weaker particle-membrane interactions may explain the insignificant influence of surface functionality and higher survival rates of particle-exposed cells. In contrast, surface functionality exerts moderate influence on LLC cell toxicity, possibly as a result of increased interaction between the TiO2 particle surface and the cell membrane. The most significant variances were seen in the JHU prostate tumor cells.



The influence of particle concentration on survival rates of cells. TiO2 particles in various concentrations were added into culture plated with confluent cells. After incubation for 24 hours the cell viability was then quantified with Live/Dead cytotoxicity Viability stain (Molecular Probes). The cell viabilities were then normalized with cells without treatment. Vertical lines denote ± 1 SD (n = 4 for all test samples and cells). Significance of differences between cancer cells versus 3T3 cells (▲)** P < .05.

The basis for the observed differential effects of surface functional groups on cell survival is mostly unclear because of the complex interaction between the cell-specific membrane properties and nanoparticle surface chemistry. The JHU prostate tumor cells showed a significant susceptibility to -NH2-coated nanoparticles. JHU cells have a relatively high cell toxicity at low particle concentrations (0.1 and 1 mg/mL), with cell survival around only 60% of that of uncoated particles. At high concentration (10 mg/mL) there is no difference of cell toxicity among -NH2-coated or uncoated nanoparticles. The detailed mechanism of such responses has yet to be determined. Because it is well established that positively charged nanoparticles have high affinity to negatively charged cell membrane protein,48 it is probable that JHU cell membranes were saturated with -NH2- functionalized particles at the lowest concentration (0.1 mg/mL) used. In addition, using polypropylene microparticles, we found that the density of surface functionality has little influence on cell-particle interactions. Therefore, the increase in the surface NH2 concentration, or the increased exposure to NH2 groups in the case of nanoparticles, may not have a significant effect on cell survival.


D.M. Blake, P.-C. Maness, Z. Huang, E.J. Wolfrum and J. Huang, Application of the photocatalytic chemistry of titanium dioxide to disinfection and the killing of cancer cells, Sep Purif Methods 28 (1) (1999), pp. 1–50.

Ref.

16 N.-P. Huang, M.-H. Xu, C.-W. Yuan and R.-R. Yu, The study of the photokilling effect and mechanism of ultrafine TiO2 particles on U937 cells, J Photochem Photobiol A: Chem 108 (2-3) (1997), pp. 229–233.

17 A.P. Zhang and Y.P. Sun, Photocatalytic killing effect of TiO2 nanoparticles on LS-174-T human colon cancer cells, World J Gastroenterol 10 (21) (2004), pp. 3191–3193.

18 C. Ogino, M. Farshbaf Dadjour, K. Takaki and N. Shimizu, Enhancement of sonocatalytic cell lysis of Escherichia coli in the presence of TiO2, Biochem Eng J 32 (2) (2006), pp. 100–105.

19 D.M. Blake, P.-C. Maness, Z. Huang, E.J. Wolfrum and J. Huang, Application of the photocatalytic chemistry of titanium dioxide to disinfection and the killing of cancer cells, Sep Purif Methods 28 (1) (1999), pp. 1–50.

20 R. Cai, Y. Kubota, T. Shuin, H. Sakai, K. Hashimoto and A. Fujishima, Induction of cytotoxicity by photoexcited TiO2particles, Cancer Res 52 (8) (1992), pp. 2346–2348.



Phagocytes


Phagocytes are cells that are found in the blood, bone marrow and other tissues of vertebrates.[1] These cells ingest and destroy foreign, particulate matter such as microorganisms and debris by a process called phagocytosis. They are important in the immunity and resistance to infection.

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