Intelligent catalase-coated MnO ₂ nanoparticles with programmed oxygen supply and glutathione depletion for enhanced photodynamic therapy

Manganese dioxide (MnO₂) nanoparticles have been reported to deliver drugs, supply oxygen and consume glutathione (GSH) to promote cancer photodynamic therapy (PDT). However, most of them suffer from low drug loading capacity and conflicting oxygen/GSH tuning, which restricts their therapeutic potential. In this study, a high capacity MnO₂-derived multifunctional nanocarrier was designed to alleviate tumor hypoxia, one of the most critical conditions for effective PDT, by systematically modulating local oxygen supply and GSH depletion. The prepared MnO₂ (MH) nanoaggregates were coated with catalase (CAT) through molecular assembly and chemical crosslinking, yielding the MH@CAT nanocomposite. In the presence of hydrogen peroxide (H₂O₂), the CAT coating facilitates oxygen generation, while the MnO₂ core remains intact until encountering intracellular GSH, resulting in MnO₂ decomposition and GSH draining. This programmed regulation of oxygen supply and GSH consumption is a key design to optimize the tumor microenvironment for enhanced PDT. After loading chlorin e6 (Ce6), the as-prepared MH@CAT-Ce6 demonstrates improved cellular uptake, oxygen self-supply, and GSH depletion - all of which contribute to the superior PDT effects observed against breast cancer cells both <i>in vitro</i> and <i>in vivo</i>. Notably, the MH@CAT-Ce6 nanoparticles exhibit excellent tumor accumulation and retention, leading to potent anti-tumor efficacy with minimal systemic toxicity.