Development of S4A–BSA–Au NPs for enhanced anti-tumor therapy of canine breast cancer

Abstract

S4A ((1R,2R,3S)-1,2-propanediol acetal-zeylenone) is one of the derivatives of zeylenone and exhibits superior cytotoxicity against the canine breast cancer cell line CIPp. However, its poor aqueous solubility and toxicity to normal tissue limit its clinical application. Therefore, in order to enhance the anticancer effect of S4A, in this article, BSA/BSA–Au-nanocluster-aggregated core/shell nanoparticles (B-BANC-NPs) were prepared by using bovine serum albumin (BSA) and HAuCl₄, and then we further synthesized S4A–BSA–Au NPs which were spherical, with a diameter of about 60 nm. In vitro cytotoxicity assessed by using CCK-8 assay demonstrated that the IC₅₀ value of the S4A–BSA–Au NPs was 10.39 μg mL⁻¹, which was not significantly different from that of S4A (10.45 μg mL⁻¹). In vitro apoptosis assay showed that the apoptosis rate of cells treated with S4A–BSA–Au NPs was 20.12%, which was significantly higher than that of the control group treated with S4A (11.3%). Notably, S4A–BSA–Au NPs were shown to effectively accumulate at tumor sites with fluorescence tracing. Besides, the effect of S4A–BSA–Au NPs on SPARC expression was determined by western blotting, and the result showed that 24 h after applying S4A–BSA–Au NPs, SPARC expression in low, middle and high dosage groups was lower than that of the control group, and the tendency showed dose dependence. The results revealed that S4A–BSA–Au NPs could effectively improve the anti-tumor activity of S4A on canine breast cancer, which may be associated with their abilities to effectively accumulate within tumor and to reduce the expression of SPARC.