Biomineralization of Copper-Celastrol Nanohybrids for Synergistic Antitumor Therapy

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.