Polyphyllin D-loaded solid lipid nanoparticles for breast cancer: Synthesis, characterization, in vitro, and in vivo studies

Polyphyllin D (PD), a steroidal saponin in Paris polyphylla, induces apoptosis via the intrinsic apoptotic pathway in different cancer types. However, emerging evidence has shown that the primary issue with PD is its structure's hemolysis and cytotoxicity. This study aimed to develop and optimize PD-loaded SLN formulation and evaluate its efficacy in breast cancer cell lines. Apoptosis, as the mechanism of cell death, was confirmed by flow cytometry following Annexin V/propidium iodide staining and western blot analysis. In in vivo studies, tumor inhibitory efficacy was compared with different doses of PD-loaded SLN on 4T1-implanted BALB/c mice. The half-maximal inhibitory concentration (IC50) of PD- loaded SLN was calculated to be 33.25 and 35.74 μg/mL for MCF7 and MDA-MB-231 cells, respectively. Flow cytometry analysis further confirmed a significant increase in apoptosis after treatment with PD- loaded SLN. When both cell lines were treated with PD-loaded SLN, Bcl2 and HSP70 proteins were down regulated, while Bax, Bad, P53, Apaf-1, p-p53 and Noxa proteins were upregulated. This effect was also confirmed by test performed on BALB/c mice in vivo. Based on results, PD-loaded SLN may be a promising breast cancer treatment, without recognizable side effects.