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United States Department of Agriculture

Agricultural Research Service

Research Project: DIETARY MODULATION OF OBESITY-RELATED CANCER BY SELENIUM Title: Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response

Authors
item Zhang, Shu -
item Luo, Yangchao -
item Zeng, Huawei
item Wang, Qin -
item Tian, Fei -
item Song, Juizhou -
item Cheng, Wen-Hsing -

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: February 10, 2011
Publication Date: December 1, 2011
Citation: Zhang, S., Luo, Y., Zeng, H., Wang, Q., Tian, F., Song, J., Cheng, W. 2011. Encapsulation of selenium in chitosan nanoparticles improves selenium availability and protects cells from selenium-induced DNA damage response. Journal of Nutritional Biochemistry. 22(12):1137-42.

Interpretive Summary: Epidemiological evidence indicates that selenium status is inversely associated with cancer risk, and results from intervention studies show that high Se intakes effectively reduce the risk of mammary, prostate, lung, colon, and liver cancer. Chitosan is an effective, naturally oriented material for synthesizing nanopolymers and exhibits preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. We have recently shown that cellular exposure to selenium compounds activates ATM-dependent DNA damage response, an early barrier of tumorigenesis. To test whether chitosan encapsulation affects the selenium-induced DNA damage response and cellular selenium level, the HCT 116 colorectal and the MRC-5 normal cells were treated with Na2SeO3 and methylseleninic acid (MSeA) encapsulated with low molecular weight chitosan. Our results demonstrate that chitosan encapsulation enhances selenium delivery into cells and suppresses selenium-induced DNA damage response. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and cancer prevention.

Technical Abstract: Selenium, an essential mineral, plays important roles in optimizing human health. Chitosan is an effective, naturally oriented material for synthesizing nanoparticles with polyanions and exhibit preferable properties such as biocompatibility, biodegradation and resistance to certain enzymes. We have recently shown that cellular exposure to selenium compounds activates ATM-dependent DNA damage responses, an early barrier of tumorigenesis. To test whether nanoencapsulation of selenium affects the selenium-induced DNA damage response and cellular selenium level, the HCT 116 colorectal and the MRC-5 normal cells were treated with Na2SeO3 and methylseleninic acid (MSeA) encapsulated in chitosan/polyphosphate nanoparticles. Analysis of cellular selenium content demonstrates that: 1) the nanoencapsulation enhances selenium levels in cells after exposure to Na2SeO3 and MSeA (1-10 µM); 2) selenium levels are greater by Na2SeO3 than by MSeA treatment; 3) selenium levels are greater in HCT 116 than in MRC-5 cells after Na2SeO3, but not MSeA exposure. Survival analysis shows that encapsulation of selenium in chitosan nanoparticles protects the cells from Na2SeO3 or MSeA induced toxicity in both MRC-5 and HCT 116 cells. Immunofluorescent analysis demonstrates that selenium-loaded chitosan nanoparticles attenuate the selenium-induced ATM phosphorylation on Ser-1981, and the extent is more pronounced in HCT 116 than in MRC-5 cells. Our results reveal features of nanoencapsulation of selenium in chitosan that enhances selenium delivery into cells and suppresses selenium-induced DNA damage response.

Last Modified: 9/1/2014