Curcumin-Loaded Polysaccharide Nanoparticles Enhance Aqueous Dispersibility and In Vitro Cytotoxicity in Breast Cancer Cell Lines

Curcumin (CUR) is a natural compound with anticancer potential; however, its poor water solubility, instability, and rapid degradation limit its therapeutic use. To address these issues, we developed CUR-loaded nanoparticles (CUR-NPs) based on chitosan, hyaluronic acid, and alginate, the TEM-measured diameter of 29.3 ± 9.0 nm. Dynamic light scattering (DLS) analysis further confirmed good aqueous dispersibility, revealing hydrodynamic diameters of 39.8 ± 7.1 nm for UL-NPs and 46.1 ± 18.1 nm for CUR-NPs. Cytotoxicity assays revealed significant anticancer activity in both MCF-7 and MDA-MB-231 cells, with IC₅₀ values of 17.5 ± 1.9 μg/mL and 39.9 ± 5.4 μg/mL after 72 h, respectively, indicating cell line-dependent sensitivity with MCF-7 cells being more susceptible to CUR-NP treatment. Time-dependent uptake was confirmed using fluorescence imaging and flow cytometry, which demonstrated faster and higher NP uptake by MCF-7 cells than by MDA-MB-231 cells. Collectively, these data support a cell line-dependent cell death response: MCF-7 cells displayed earlier and more pronounced changes consistent with apoptosis, whereas MDA-MB-231 cells showed slower uptake with delayed apoptosis and partial necrosis. Subcellular localization dynamics, particularly perinuclear aggregation, have emerged as determinants of NP-induced cytotoxicity, highlighting the potential for tailoring NP design to specific cellular contexts to improve therapeutic efficacy.