Heterogeneous inorganic nanomedicine delivery system loaded with anlotinib for enhanced treatment of non-small cell lung cancer (NSCLC)

Non-small cell lung cancer (NSCLC) poses a formidable therapeutic challenge due to drug resistance and limited treatment efficacy. To address this, we developed a novel nanodrug delivery system, SPIO@SiO 2 -ANB, which integrates superparamagnetic iron oxide nanoparticles (SPIOs), a silica (SiO 2 ) shell, and the surface-loaded multi-target tyrosine kinase inhibitor anlotinib (ANB). This platform enhances drug stability, enables tumor-targeted delivery, and induces ferroptosis. The synthesized nanoparticles demonstrated a monodisperse spherical morphology, pH-responsive ANB release, and efficient cellular internalization. In vitro, SPIO@SiO 2 -ANB exhibited superior cytotoxicity against A549 and H460 NSCLC cells compared to free ANB, concurrently elevating intracellular reactive oxygen species (ROS) and modulating key ferroptosis-related proteins (COX-2, xCT, GPX4). In vivo studies using xenograft models revealed improved tumor accumulation and retention of SPIO@SiO 2 -ANB, leading to significant tumor growth inhibition, enhanced apoptosis, and suppressed angiogenesis. This work presents a synergistic therapeutic strategy that combines ferroptosis induction with targeted therapy, offering a promising avenue for the safe and effective treatment of NSCLC. • A novel SPIO@SiO 2 -ANB nanoplatform was developed for NSCLC therapy • The system combines ANB targeted therapy with SPIO-induced ferroptosis • pH-responsive drug release enables tumor-specific delivery of anlotinib • SPIO@SiO 2 -ANB shows enhanced anti-tumor efficacy and good biosafety