Multifunctional Inulin-Coated Gold Nanoparticles for Targeted Breast Cancer Theranostics with ROS-Amplified Photothermal Therapy

The integration of diagnostic and therapeutic modalities into a single, biocompatible vehicle represents a frontline strategy in precision oncology. This study evaluates the biological efficacy and molecular mechanism of a novel, biodegradable, multifunctional nanoplatform consisting of curcumin (CUR) and the near-infrared dye IR-780 co-loaded into an inulin-coated gold nanoparticle matrix (INU–CUR–IR780–AuNP). Synthesized to overcome the poor pharmacokinetics of free curcumin and harness the localized surface plasmon resonance (LSPR) of metallic cores, the nanoplatform was systematically tested against human breast adenocarcinoma (MCF7) cells. Quantitative fluorescence tracking confirmed high intracellular accumulation via clathrin-mediated endocytosis, directed by the hydrophilic inulin shell. Under continuous-wave 808 nm near infrared (NIR) laserirradiation (1.0 W/cm², 5 min), the nanoplatform exhibited exceptional photothermal conversion, inducing localized hyperthermia alongside a massive 3.5-fold spike in intracellular reactive oxygen species (ROS) fluorescence intensity (1.68 ± 0.10 compared to 0.48 ± 0.02 in controls; p < 0.001). This oxidative and thermal surge drove a synergistic drop in MCF-7 cell viability to 13.5%, significantly outperforming free payloads and non-irradiated controls. Flow cytometric profiling using Annexin V-FITC/PI confirmed that death occurred cleanly through programmed apoptosis (78.2%) rather than non-specific necrosis. Mechanistically, the ROS cascade and thermal stress collapsed the mitochondrial membrane potential (ΔΨm), triggering the cytosolic release of Cytochrome c, assembly of the APAF-1/caspase-9 apoptosome, and the subsequent activation of Caspase-3.Downstream execution was confirmed by the precise proteolytic inactivation of poly (ADP-ribose) polymerase (PARP) into its hallmark 89 kDa and 24 kDa fragments, preventing genomic repair. These findings demonstrate that the INU–CUR–IR780–AuNP platform acts as an integrated, highly effective system for image-guided, ROSamplified photothermal eradication of breast cancer cells.