Abstract 4476: Curcumin gold nanoparticles significantly boost the effectiveness of docetaxel-induced apoptosis in breast cancer

Abstract Breast cancer (BrCa) is the most diagnosed cancer in women; it develops locally and then metastasizes to other organs. Due to tumor heterogeneity, the prevalence of drug resistance, and disease recurrence, current therapy options are proving less effective for specific BrCa subtypes, such as triple-negative breast cancer (TNBC). Therefore, BrCa treatment has shifted from a one-size-fits-all strategy to a more focused approach. In this study, we demonstrated folate receptor-based targeted delivery of either curcumin (Cur), a natural compound isolated from Curcuma longa, or docetaxel (DTX), a chemotherapeutic drug, or a combination of the two, using gold nanoparticles (AuNPs) for successful BrCa therapy. We synthesized AuNPs coated with folic acid (FA)-conjugated with poly (ethylene glycol) copolymer, encapsulated with DTX and Cur, and then characterized these NPs for size, charge, shape, conjugation, and distribution using various techniques, including a Zetasizer, scanning electron microscope (SEM), transmission electron microscope (TEM), nuclear magnetic resonance (NMR), and nanoparticle tracking analysis (NTA). The results confirmed the successful conjugation of both drugs. To evaluate whether Cur enhanced the efficacy of DTX-AuNPs on BrCa cell lines (MCF-7 and MDA-MB-231), we treated the cells with Cur- or DTX- alone or in combination -AuNP followed by cell viability assessment using MTT assay and apoptosis assays. The live/dead cells immunofluorescence test confirms the effectiveness of combined drugs, showing an increase in dead nuclei in MCF-7 and MDAMB 231 cells treated with the combination (FA-Cur+ DTX-AuNP) for 48 hours. The combination was most effective in inducing apoptosis, inhibiting EMT (epithelial-mesenchymal transition), and BrCa cell proliferation. It showed the downregulation of the anti-apoptotic Bcl-xL and the upregulation of pro-apoptotic markers Bak and Bid. The EMT markers, E-cadherin, were upregulated, and the N-cadherin and Snail markers were downregulated in western blots and RT-PCR. Further, the combination of NPs increases the expression of p27KIP1, inhibiting the CDK4, Cyclin D1 complex and the transition of cells into G0/G1 to the S phase in both cell lines. The NPs internalization, colony formation, and migration assays further confirm the synergistic effect of both NPs. These findings indicate that Cur may serve as a therapeutic contender for enhancing the effectiveness of DTX, representing a promising advancement in breast cancer treatment. Citation Format: Santosh K. Singh, Rajesh Singh. Curcumin gold nanoparticles significantly boost the effectiveness of docetaxel-induced apoptosis in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4476.