Mineral–Herb Nanohybrids Generated through Endogenous Nanogenesis for Multimodal Imaging-Guided Renal Cancer Therapy

Abstract Decoction-derived nanoparticles have recently emerged as a class of naturally derived biomaterials, but their biomedical utility remains largely limited by the lack of intrinsic imaging capability. Here, we demonstrate that incorporating mineral medicines into traditional mineral–herb decoctions enables an endogenous nanogenesis process that spontaneously generates organic–inorganic nanohybrids with inherent magnetic resonance and photoacoustic imaging functions. Using corni fructus and magnetitum as a model system, we reveal that herbal ligands continuously mediate mineral dissolution, coordination reconstruction, and hierarchical reassembly through a ligand-directed dissolution–assembly mechanism, ultimately producing stable mineral–herb nanohybrids. Importantly, this endogenous nanogenesis strategy is further validated across multiple mineral–herb combinations, demonstrating its general applicability. The resulting corni fructus–magnetitum nanohybrids (N-CFM) enable dual-modal imaging of renal tumors while simultaneously inducing oxidative stress-associated ferroptotic and apoptotic responses after systemic administration. In parallel, N-CFM remodels the tumor immune microenvironment through macrophage polarization and enhanced cytotoxic T-cell infiltration, resulting in effective suppression of orthotopic tumor progression and metastasis with favorable biocompatibility. This work expands the functional boundary of decoction-derived biomaterials by introducing intrinsic imaging capability through mineral integration and provides a general strategy for developing naturally derived theranostic biomaterials for imaging-guided cancer therapy.