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Size‐Transformable Supramolecular Nanoprodrugs Enable Redox Imbalance Amplification and Cholesterol Modulation to Boost Multidimensional Tumor Immunotherapy

Researchers have engineered a tumor‑targeting, tumor‑microenvironment‑responsive supramolecular nanoprodrug that switches size to enhance deep tumor penetration. The nanoprodrug simultaneously induces redox imbalance—accumulating reactive nitrogen species and depleting glutathione—to amplify ferroptosis, while depleting cholesterol to rejuvenate exhausted T cells. This multidimensional approach triggers immunogenic cell death, activates the tumor immune cycle, and suppresses both primary and distant tumors. It also establishes durable systemic immunity that prevents recurrence.