Self-assembled drug-loading platform of copper-based MOFs composite particles: Synergistic enhancement of laryngeal squamous cell carcinoma suppression via cuproptosis and microtubule arrest

The integration of novel regulatory pathways for cell death with conventional chemotherapy provides a new approach for cancer treatment. Therefore, we constructed a self-assembled nano drug platform (CuT@DOC) by combining a copper-based metal-organic framework (CuT) and docetaxel (DOC), aiming to synergistically enhance the inhibitory effect on laryngeal squamous cell carcinoma (LSCC). The CuT@DOC has been confirmed to have a unique “sphere-sheet” hybrid morphology, high stability, and efficient drug loading through a series of structural characterizations. In addition, the CuT@DOC catalyze strong ROS generation and glutathione depletion under tumor-mimicking acidic and H₂O₂-rich environments. Therefore, the CuT@DOC significantly enhanced oxidative stress via continuous Cu²⁺/Cu⁺ cycling, amplifying ROS accumulation and triggering cuproptosis. Concurrently, DOC preserved its microtubule-targeting function, inducing pronounced G2/M arrest. The integration of these mechanisms led to synergistic cytotoxicity against LSCC cells, with markedly reduced toxicity in normal fibroblasts and epithelial cells. The CuT@DOC also exhibited superior therapeutic efficacy and selectivity, underscoring the advantage of combining chemotherapy with copper-dependent cell death in a single nanoplatform. This work proposes CuT@DOC as a robust and biocompatible nanoplatform that leverages dual mechanisms cuproptosis and microtubule disruption to achieve potent and selective tumor inhibition. This study will provide experimental and theoretical support for multimodal nanotherapeutic strategies, offering a promising direction for the precision treatment of LSCC and potentially broader head and neck malignancies.