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However, clinical translation faces several challenges: difficulties in large-scale production of complex nanostructures requiring precise control of layered compositions (118), systemic oxidative damage (e.g., hepatotoxicity) caused by free iron ions (137), long-term retention issues of certain metal nanoparticles (138), potential complement system activation or inflammatory responses triggered by nanoparticles (139) and limited delivery efficiency due to tumor stromal barriers and immunosuppressive TME (140)

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Across all withheld metabolites, the most frequently generated structure matched that of the held-out metabolite in 29% of cases (Fig