Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells through PARP cleavage

[Display omitted] •Lipid polymer hybrid nanoparticles were successfully designed by DoE approach.•The optimum formulation was selected through 32 full factorial design approach.•Cucurbitacin B, a natural compound, was encapsulated into the synthesized nanoparticles.•CuB-NP inhibited cell growth through G0/G1 arrest and induced apoptosis through PARP cleavage.•A better anticancer efficiency has been achieved by CuB–NP compared to compound alone. 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.