In the present study, we developed the lipid polymer hybrid nanoparticles of cucurbitacin B (CuB) and evaluated its effects on triple negative breast cancer cells. The 32 factorial design was utilized to understand the influence of input variables including PEG-conjugated phospholipid/biodegradable polymer ratio and the total lipids/lecithin molar percentage ratio. The hybrid formulation at the center point of design was specified as optimal hybrid nanocarrier due to its superior features. CuB loaded nanoparticles (CuB-NP) inhibited cell growth through a cell cycle arrest at G0/G1 phase. The studies investigating the efficacy of CuB-NP on apoptosis of cancer cells showed that the annexin v-bound cell population was 20.66 ± 1.99%, and the depolarized cell population was higher in CuB-NP treated cells. The pro-apoptotic bax, Iκb-α and cleaved PARP levels increased in CuB-NP treated cells, while anti-apoptotic Bcl-2 and NF-κB levels decreased. The caspase (+) cell population was higher in nanoparticle-treated group as 14.20 ± 0.56% and the findings obtained from the caspase assay were also compatible with western blot data. Overall, both CuB and CuB-NP demonstrated anticancer activity, while the lipid polymer hybrid nanoparticle formulation of CuB indicated that the nanoparticle formulation has more promising effect for the treatment of breast cancer.
Keywords: Apoptosis; Breast cancer; Cucurbitacin B; DoE approach; Hybrid nano-carrier.
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