Kirkendall Effect-Driven Construction of Hollow Rare-Earth Silicate Nanospheres for Drug Loading

Abstract Monodisperse oxide nanoparticles have attracted attention for biomedical applications. However, conventional synthetic methods often provide limited control over particle size, morphology, and polydispersity. Herein, we report a bottom-up strategy for synthesizing hollow rare-earth silicate nanospheres based on the Kirkendall effect. The addition of an optimized amount of 1-propanol to the reaction medium altered the dielectric constant and surface tension, thereby increasing the nucleation rate and reducing the precursor size. During high-temperature treatment, unequal interdiffusion of rare-earth and silicon atoms across the phase interface induced the Kirkendall effect and generated internal voids approximately 50 nm in size for drug loading. DOX-loaded nanospheres exhibited acid-responsive release and cytotoxicity, whereas RB-loaded nanospheres generated singlet oxygen under X-ray irradiation and induced cell death. These findings demonstrate the potential of hollow rare-earth silicate nanospheres as platforms for drug delivery and X-ray-induced photodynamic therapy.