Nanopartículas de Bismuto (Bi) No Estequiométricas y Multivalentes como Agentes Terapéuticos para el Tratamiento...

Defect engineering in nanoparticulate metal oxides through oxygen vacancies and metal multivalency has been shown to promote pH-dependent ROS generation and selective oxidative stress in malignant cells. Coupling this behavior with the strong X-ray attenuation of heavy elements allows the development of theranostic nanomaterials with computed tomography (CT) imaging. Accordingly, we synthesized two forms of multivalent bismuth (Bi)-based nanospheres (Bi@BiO_x and Bi₂O_3-x) as theranostic agents for melanoma treatment. Melanoma is the deadliest form of skin cancer, and current treatment regimens are hindered by poor selectivity and incomplete tumor eradication. Bi@BiO_x was synthesized via a hydrothermal method and annealed to obtain Bi₂O_3-x. Both materials consisted of ∼115 nm nanospheres containing oxygen vacancies and multivalent Bi atoms. Featuring notable CT imaging properties, with CT contrast enhancement efficiencies of 12.9 (Bi@BiO_x) and 14.3 (Bi₂O_3-x) Hounsfield Units mL mg^-1. In vitro assays revealed selective cytotoxicity toward human melanoma A375 cells over nonmalignant HaCaT cells. At 50 μg mL^-1, Bi@BiO_x and Bi₂O_3-x reduced A375 colony formation by 93% and 63%, respectively. Time-course cell death was associated with higher ROS accumulation in A375 cells (4.5 ± 0.4-fold (Bi@BiO_x) and 2.8 ± 0.2-fold (Bi₂O_3-x)) compared to HaCaT cells (2.1 ± 0.2 and 1.60 ± 0.03-fold). Apoptotic populations in A375 cells reached ∼35% (Bi@BiO_x) and ∼16% (Bi₂O_3-x), vs ∼7% in HaCaT cells. Greater LDH release in A375 cells further supported ROS-mediated cytotoxicity. This work highlights the potential of Bi@BiO_x and Bi₂O_3-x as versatile theranostic agents for CT-guided melanoma therapy, exploiting defect-engineered nanochemistry for spontaneous, cancer-selective oxidative stress induction.