Polymeric nanocapsules prevent oxidation of core-loaded molecules: evidence based on the effects of docosahexaenoic acid and neuroprostane on breast cancer cells proliferation

International audienceBackground:Nanocapsules, as a delivery system, are able to target drugs and other biologically sensitive moleculesto specific cells or organs. This system has been intensively investigated as a way to protect bioactives drugs frominactivation upon interaction with the body and to ensure the release to the target. However, the mechanism ofimproved activity of the nanoencapsulated molecules is far from being understood at the cellular and subcellularlevels. Epidemiological studies suggest that dietary polyunsaturated fatty acids (PUFA) can reduce the morbidityand mortality from breast cancer. This influence could be modulated by the oxidative status of the diet and it hasbeen suggested that the anti-proliferative properties of docosahexaenoic acid (DHA) are enhanced by pro-oxidantagents Methods:The effect of encapsulation of PUFA on breast cancer cell proliferation in different oxidative mediumwas evaluated in vitro. We compared the proliferation of the human breast cancer cell line MDA-MB-231 and ofthe non-cancer human mammary epithelial cell line MCF-10A in different experimental conditions. Results:DHA possessed anti-proliferative properties that were prevented by alpha-tocopherol (an antioxidant) andenhanced by the pro-oxidant hydrogen peroxide that confirmsthat DHA has to be oxidized to exert its anti-proliferativeproperties. We also evaluated the anti-proliferative effects of the 4(RS)-4-F4t-neuroprostane, a bioactive, non-enzymaticoxygenated metabolite of DHA known to play a major role inthe prevention of cardiovascular diseases. DHA-loadednanocapsules was less potent than non-encapsulated DHA while co-encapsulation of DHA with H2O2maintainedthe inhibition of proliferation. The nanocapsules slightly improves the anti-proliferative effect in the case of4(RS)-4-F4t-neuroprostane that is more hydrophilic than DHA. Conclusion:Overall, our findings suggest that the sensitivity of tumor cell lines to DHA involves oxidized metabolites.They also indicate that neuroprostane is a metabolite participating in the growth reducing effect of DHA, but it is not thesole. These results also suggest that NC seek to enhance the stability against degradation, enhance cellular availability,and control the release of bioactive fatty acids following their lipophilicities