Integrating green chemistry into SPION development: a theranostic study on prostate cell models

Superparamagnetic iron oxide nanoparticles (SPIONs) represent versatile building blocks for multimodal theranostics. Here, Fe₃O₄@Au@Gd hybrid nanoplatforms synthesised via a green approach using Nymphaea alba leaf extract were systematically compared with their dextran-coated counterparts prepared by a conventional route. Structural and magnetic analyses confirmed comparable iron oxide crystallite sizes (∼18 nm) for both methods, while PIXE quantification revealed substantially enhanced gadolinium (Gd) incorporation for the green-synthesised systems, reaching ∼23% for the SP-LV-Au1-Gd formulation. The samples exhibit dual therapeutic activity through distinct, composition-dependent mechanisms. Radiosensitisation under ⁶⁰Co γ-irradiation is dominated by the gold (Au) shell and is associated with increased reactive oxygen species (ROS)-mediated cytotoxicity and ultrastructural damage in human prostate cancer (PC3) cells. In contrast, magnetic hyperthermia (MH) efficiency, quantified by the specific absorption rate, is markedly enhanced by Gd incorporation, which increases magnetic disorder and effective core size, thereby improving heat dissipation. MH-induced cytotoxicity is efficient and selective towards PC3 cells relative to normal RWPE-1 cells and occurs independently of ROS generation. Relaxometric measurements indicate that, despite substantial Gd inclusion, the strong transverse relaxivity of the iron oxide core yields predominantly T₂-weighted MRI contrast. These green-synthesised SPION-Au-Gd nanohybrids thus offer a sustainable, composition-tunable platform for integrated prostate cancer theranostics.