Modulation of tumor microenvironment by metal-organic-framework-derived nanoenzyme for enhancing nucleus-targeted photodynamic therapy

Photodynamic therapy (PDT) is a promising strategy for tumor treatment. Still, its therapeutic efficacy is compromised by the unsatisfactory cytotoxicity to specific subcellular organelles and insidious tumor microenvironment properties like hypoxia and high glutathione levels. Here, we fabricated a novel nanoenzyme that derived from metal-organic framework (MOF) with intrinsic catalase-like activities to decompose H₂O₂ to O₂ and simultaneous glutathione consumption for enhancing PDT efficacy. The obtained Mn₃O₄ nanoparticle shows a larger pore size and surface area compared to native MOF particles, which can be used to load high dose photosensitizer. When decorated with AS1411 aptamer and polyethylene glycol (PEG), the obtained Mn₃O₄-PEG@C&A particle exhibits excellent stability and cell nucleus targeting ability. Remarkably, Mn₃O₄-PEG@C&A particle inhibited the tumor growth in the mouse model with high efficacy without any biotoxicity. This is the first report that applied MOF-derived nanoparticle to nucleus-targeted PDT. It may provide a new approach for designing functional nanoenzyme to subcellular organelles-targeted tumor modulation.