Facile fabrication of combination delivery of kaempferol and sorafenib with PEGylated gold nanoparticles delivery to breast cancer: Investigation of cytotoxicity and apoptosis induction

Abstract

Abstract Current clinical therapies for invasive breast cancer have low therapeutic effectiveness and substantial systemic adverse effects, leading to poor patient compliance. In this investigation, we developed dual anticancer drugs (sorafenib (SFB) and kaempferol (KMF)) encapsulated in PEGylated gold nanomaterial (PEG-AuNPs@SFB/KMF) for a drug delivery system targeting breast cancer to circumvent this problem. Subsequent research examined whether pH affects drug release. The current study results show that sorafenib and kaempferol work better together than each treatment individually in eliciting cytotoxic effects. In vitro cytotoxicity studies confirmed that PEG-AuNPs@SFB/KMF were more effective than sorafenib alone in MCF-7 and MDA-MB-231 cells, with less toxicity in NIH3T3 cells. The cancer cell proliferation was measured by Click-iT EdU assay, which indicates that the NPs effectively induce apoptosis in cancer cells. The different biochemical staining (acridine orange and ethidium bromide (AO-EB and nuclear staining (DAPI)) methods confirmed the morphological investigation of the cells. PEG-AuNPs@SFB/KMF increased apoptosis ratio, confirmed by flow cytometric analysis via Annexin V-FITC/PI staining methods. Therefore, we believe that the built multifunctional nanocarrier based on developed nanoparticle delivery could be an alternative therapeutic strategy for breast cancer therapy. Graphical Abstract