Nanoparticles Loaded with the BET Inhibitor JQ1 Block the Growth of Triple Negative Breast Cancer Cells In Vitro and In Vivo

Cancers - Tập 12 Số 1 - Trang 91
Valentina Maggisano1, Marilena Celano1, Rocco Malivindi2, Ines Barone2, Donato Cosco1, Catia Mio3, Chiara Mignogna4, Salvatore Panza2, Giuseppe Damante3, Massimo Fresta1, Sebastiano Andò2, Diego Russo1, Stefania Catalano2, Stefania Bulotta1
1Department of Health Sciences, “Magna Graecia” University of Catanzaro, 88100, Catanzaro, Italy
2Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Cosenza, Italy;
3Department of Medical Area, University of Udine, 33100 Udine, Italy
4Interdepartmental Service Center, "Magna Graecia" University of Catanzaro, 88100 Catanzaro, Italy;

Tóm tắt

Inhibition of bromo-and extra-terminal domain (BET) proteins, epigenetic regulators of genes involved in cell viability, has been efficiently tested in preclinical models of triple negative breast cancer (TNBC). However, the use of the selective BET-inhibitor JQ1 on humans is limited by its very short half-life. Herein, we developed, characterized and tested a novel formulation of nanoparticles containing JQ1 (N-JQ1) against TNBC in vitro and in vivo. N-JQ1, prepared using the nanoprecipitation method of preformedpoly-lactid-co-glycolic acid in an aqueous solution containing JQ1 and poloxamer-188 as a stabilizer, presented a high physico-chemical stability. Treatment of MDA-MB 157 and MDA-MB 231 TNBC cells with N-JQ1 determined a significant decrease in cell viability, adhesion and migration. Intra-peritoneal administration (5 days/week for two weeks) of N-JQ1 in nude mice hosting a xenograft TNBC after flank injection of MDA-MB-231 cells determined a great reduction in the growth and vascularity of the neoplasm. Moreover, the treatment resulted in a minimal infiltration of nearby tissues. Finally, the encapsulation of JQ1 in nanoparticles improved the anticancer efficacy of this epigenetic compound against TNBC in vitro and in vivo, opening the way to test it in the treatment of TNBC.

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