Metal-coordination-driven self-assembly of 8-hydroxyquinoline-peptide into hybrid nanomaterials for in vitro...

Hybrid nanomaterials based on 8-hydroxyquinoline (8-HQ) metal complexes represent a promising class of therapeutic platforms, combining high biocompatibility with diverse pharmacological activities. Leveraging the strong bidentate metal-chelating ability of 8-HQ, we designed and synthesized a bioactive self-assembling molecule (HQD) by conjugating an 8-HQ unit with a peptide assembly motif. Driven by non-covalent interactions and metal-ion coordination (Fe³⁺, Cu²⁺, Mn²⁺), HQD undergoes supramolecular self-assembly in aqueous solution to form hybrid nanomaterials with excellent biocompatibility. While HQD_Fe and HQD_Mn exhibit higher photothermal conversion efficiency, HQD_Cu demonstrates superior multifunctional catalytic activities, including efficient reactive oxygen species (ROS) generation, glutathione (GSH) depletion, and DNA cleavage via intercalation and groove binding. Additionally, the strong near-infrared absorption and efficient photothermal effect of HQD_Cu further disrupt redox homeostasis, amplify oxidative stress, and promote cancer cell apoptosis. Importantly, doxorubicin-loaded HQD_Cu nanoparticles (HQDCuD) enhance cellular uptake and exert a potent in vitro anticancer effect through the synergistic integration of chemotherapy, photothermal therapy, and ROS-mediated oxidative damage, establishing a powerful multimodal platform for in vitro cancer treatment studies.