Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines

Article Article scientifique Article Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines eng 2021 author Dupertuis Yves Marc 0000-0003-4891-0487 24489 author Boulens Nathalie 130558 author Angibaud Emmanuelle 803219 author Briod Anna-Sophia author Viglione Alexandre 747236 author Allémann Eric 0000-0002-6598-9521 26730 author Delie Salmon Florence 121330 author Pichard Claude 21908 10.1208/s12249-020-01897-5 33404935 1530-9932 http://link.springer.com/10.1208/s12249-020-01897-5 It has been shown that long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs)could act synergistically with 5-fluorouracil (5-FU) to kill cancer cells. To facilitate their simultaneous transport in the bloodstream, we synthesized, for the first time, liposomes (LIPUFU) containing 5-FU in the aqueous core and docosahexaenoic acid (DHA)/ eicosapentaenoic acid (EPA) at a ratio of 1:2 in the lipid bilayer. LIPUFU werestable with uniform size of 154 ± 4 nm, PDI of 0.19 ± 0.03 and zeta potential of -41 ± 2 mV. They contained 557 ± 210 μmol/l DHA, 1467 ± 362 μmol/l EPA, and 9.8 ± 1.1 μmol/l 5-FU. Control liposomes without (LIP) or with only 5-FU (LIFU) or n-3 PUFAs (LIPU) were produced in a similar way. The effects of these different liposomal formulations on the cell cycle, growth, and apoptosis were evaluated in two human colorectal cancer (CRC) cell lines differing in sensitivity to 5-FU, using fluorescence-activated cell sorting analyses. LIPUFU were more cytotoxic than LIP, LIFU, and LIPU in both LS174T (p53+/+, bax−/−) and HT-29 (p53−/0, bax+/+) cell lines. Similar to LIFU, LIPUFU increased the percentage of cells in S phase, apoptosis, and/or necrosis. The cytotoxic potential of LIPUFU was confirmed in vivo by tumor growth inhibition in the chicken chorioallantoic membrane model. These results suggest that LIPUFU could be considered to facilitate the simultaneous transport of 5-FU and n-3 PUFAs to the tumor site, in particular in case of CRC liver metastases. Colorectal cancer Chemotherapy 5-fluorouracil Polyunsaturated fatty acids Liposomes Dewey 615 Dewey 616 31 Section des sciences pharmaceutiques 17 56 Département de médecine 221 false 883 Technologie pharmaceutique 1386 Nutrition et chronobiologie 1038 AAPS PharmSciTech 22 1 8a9656d7-73a8-4acb-b655-9c93aa1cd9d7 Article (Published version) Public Dupertuis_AAPS_2021_Article_AntitumorEffectOf5-Fluorouraci.pdf 2689935 application/pdf CC BY openAccess Faculté des sciences / Section des sciences pharmaceutiques Faculté de médecine / Section de médecine clinique / Département de médecine

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Antitumor Effect of 5-Fluorouracil-Loaded Liposomes Containing n-3 Polyunsaturated Fatty Acids in Two Different Colorectal Cancer Cell Lines	AAPS PharmSciTech			2021	360	124

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Angibaud, Emmanuelle