An effective photothermally active titanium-copper nanocomposite for breast cancer therapy

Cancer therapy faces several challenges including metastasis, subsequent recurrence and the high susceptibility of immunocompromised patients to secondary bacterial infections. In this study, a copper-doped titanium dioxide nanocomposite (Ti-Cu NC) was developed as a multifunctional photothermal agent for breast cancer treatment. In 4T1 murine breast cancer cells, Ti-Cu NCs induced significant (approximately 3.8-fold increase compared to control) reactive oxygen species (ROS) production, leading to apoptosis and cell death with a synergistic effect observed upon near-infrared (NIR) irradiation (1.5 W cm^-2, 10 min). The nanocomposites also reduced the migratory capacity of 4T1 cells, indicating potential anti-metastatic activity. Importantly, Ti-Cu plus NIR irradiation triggers immunogenic cell death (ICD) markers in cancer cells, suggesting the ability to activate host antitumor immunity against residual and metastatic cancer cells. Beyond anticancer effects, the synergistic photothermal activity of Ti-Cu NCs effectively suppressed bacterial growth. Antibacterial rates of 99.57%, 99.4%, 99.6%, and 98.3% were recorded for MRSA, K. pneumoniae, E. coli, and P. aeruginosa, respectively, at a concentration of 300 µg mL^-1. At a concentration of 1000 µg mL^-1, the antibacterial rate was 100% for all four pathogenic strains in the presence of NIR, addressing the clinical challenge of cancer-related infections. In vivo, Ti-Cu NCs combined with NIR irradiation demonstrated potent anticancer efficacy (temperature rise to ∼44.5 °C, significant tumor growth inhibition) with no detectable toxicity following intraperitoneal injection, even at higher doses. These findings establish Ti-Cu NCs as a safe, biocompatible, and dual-functional platform that induces ROS-mediated apoptosis, suppresses tumor cell migration, triggers immunogenic cell death, and eliminates bacteria via photothermal synergy, highlighting their potential as promising candidates for integrated cancer immunotherapy and infection control.