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A Carbon-Based Nanozyme Derived from Traditional Chinese Medicine Triggers Lysosome-Mediated Ferroptosis and Sensitizes Oral Cancer to Anti-PD-1 Therapy
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DOI：10.1016/j.carbon.2026.121651.png)
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Abstract
En 中文
Resistance to immune checkpoint blockade (ICB) in head and neck squamous cell carcinoma is strongly linked to a GPX4-high metabolic state that fosters an immunologically "cold" microenvironment. Here, we demonstrate a strategy to overcome this by transforming a complex traditional Chinese medicine (TCM) formula into a potent, lysosome-targeting carbon-based nanozyme (H-CDs). Synthesized via a simple hydrothermal method, the H-CDs possess an N-doped carbon framework with intrinsically coordinated, atomically dispersed Fe3+ catalytic centers derived from the herbal precursors. Upon accumulation in acidic lysosomes, these nanozymes are activated to catalytically deplete glutathione (Km = 0.133 mM) and generate hydroxyl radicals, triggering lysosomal membrane permeabilization as an upstream event for canonical ferroptosis. This process releases damage-associated molecular patterns, promoting dendritic cell maturation and CD8+ T-cell infiltration, thereby converting immunologically "cold" tumors into "hot" ones. In a syngeneic oral cancer model, combination therapy with H-CDs and an anti-PD-1 antibody achieved a synergistic 87% tumor growth inhibition. This work not only presents a powerful nanozyme for combination immunotherapy but also establishes a framework for rationally designing catalytic nanomedicines from complex, sustainable biomass.
Keywords:
Nanozyme
Ferroptosis
Lysosome
Immune checkpoint blockade
Oral cancer
Journal
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11.6
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2.0W
Citations:
10.5W
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Cited Papers