Biomineralization of Copper‐Celastrol Nanohybrids for Synergistic Antitumor Therapy

Abstract The therapeutic potential of celastrol (Cel) in cancer treatment has been constrained by its intrinsic hydrophobicity and the lack of efficient delivery systems. Herein, a biomineralization‐based strategy is introduced to construct hybrid nanoparticles (Cel‐TA‐Cu NP) via Cel‐Cu²⁺ coordination, followed by TA‐Cu²⁺ crosslinking. Biomineralization, a nature‐inspired process facilitating the controlled assembly of inorganic–organic structures, enables Cel to form coordination complexes with Cu²⁺, which subsequently serve as nucleation sites for tannic acid‐mediated copper mineralization. Unlike conventional nanocarriers, this approach exploits the intrinsic metal‐binding capacity of Cel to induce spontaneous mineralization, where Cu²⁺ serves both as a coordination center for drug encapsulation and as a therapeutic agent for chemodynamic therapy (CDT). The pH‐responsive dissociation of metal‐phenolic coordination ensures tumor‐specific drug release, while the biomineralization process inherently enhances aqueous stability and bioavailability. Moreover, the rational design of Cel‐TA‐Cu NP enables a synergistic anticancer effect by simultaneously triggering apoptotic signaling pathways and amplifying oxidative stress‐induced cytotoxicity. Overall, this biomineralization‐based nanoplatform not only overcomes the inherent limitations of Cel but also integrates CDT to markedly enhance therapeutic efficacy, providing a promising avenue for advanced cancer treatment.