Self-Detoxifying Nanocatalytic Medicine CaO2@Cu-BAL for Enhanced Chemodynamic Therapy of Tumor
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Copper ions (Cu + /Cu 2+ ) serve as catalysts in Fenton-like reactions, representing a notable alternative and supplement to the conventional iron-based (Fe 2+ /Fe 3+ ) Fenton process. The copper-based Fenton system offers several practical advantages: it operates over a broader pH range, maintains catalytic activity even under neutral conditions, and exhibits a higher reaction rate constant for the Cu + /H 2 O 2 system compared to the Fe 2+ /H 2 O 2 system. However, accumulation of copper ions in vivo can lead to hepatotoxicity and neurotoxicity, and may even cause Wilson's disease. To address this limitation, we developed a nanocatalytic medicine designated as CaO 2 @Cu-BAL, which integrates copper-based Fenton-like catalysis with a self-detoxification mechanism. The pH-responsive Cu-BAL shell encapsulates CaO 2 , ensuring stability under physiological conditions (pH 7.4) while facilitating controlled H 2 O 2 release and ·OH generation upon exposure to acidic lysosomal environments (pH 4.5-5.0). This process promotes lysosomal membrane permeabilization through lipid peroxidation. Following therapeutic action, British Anti-Lewisite (BAL) ligands mediate efficient copper chelation, facilitating rapid renal clearance and thereby reducing systemic toxicity of copper ions. This dual-functional approach synergistically enhances both the efficacy and biosafety of chemodynamic therapy (CDT), offering a promising strategy to overcome key challenges associated with metal-based nanotherapeutics.
