Development of an advanced drug delivery system to prevent and treat breast cancer bone metastasis

Abstract

Breast cancer (BC) is the most common malignancy in women, with triple-negative BC (TNBC) comprising 15–20% of cases. TNBC lacks ER, PR, and HER2 receptors, making it unresponsive to targeted therapies; doxorubicin (Dox) remains the main treatment, though limited by toxicity and resistance. Curcumin (Cur) shows anticancer potential but suffers from low bioavailability. We developed a dual-drug nanocarrier co-delivering Cur and Dox, using alendronate (ALN) for bone targeting and LHRH for tumor specificity. Pluronic F127-based micelles and niosomes were optimized to enhance drug stability and delivery. F127 integration (Span 60:F127:Cholesterol, 0.99:0.01:1) improved encapsulation efficiency (EE%): Dox EE% rose to 58.6% and Cur to 98% in F127-containing niosomes (CDFN), compared to 18.3% and 30.1% in controls. FTIR and XPS confirmed successful ligand conjugation. DLS/SEM showed particle sizes of 20–32 nm for micelles and 244.6 nm for CDFN. Zeta potential shifted from –26.2 mV (F127) to –10.3 mV (PEGylation), indicating stability. [k⁶(Ahx)]-LHRH-Cur micelles showed the lowest IC₅₀ (3.2 µM), and CDFN had superior cytotoxicity (IC₅₀ = 0.7671 µM) vs. free Dox (5.48 µM) and Cur (124.6 µM), with a synergistic CI of 0.271. In 3D spheroids, CDFN caused near-complete disintegration by day 4. Calcium-binding assays confirmed ALN-mediated bone targeting (p < 0.0001). CDFN remained stable for 7 days at room temperature and released drugs faster at acidic pH. This dual-drug system shows enhanced efficacy and selectivity, offering a promising strategy for breast cancer and bone metastasis treatment.