Calcium-peroxide-mediated cascades of oxygen production and glutathione consumption induced efficient photodynamic and photothermal synergistic therapy

Photodynamic therapy (PDT) and photothermal therapy (PTT) are potent approaches to cancer treatment. However, the tumor microenvironment (TME) characterized by severe hypoxia and abundant glutathione (GSH) significantly reduces the effectiveness of PDT. In this study, we developed an oxidative stress amplifier CaO₂/ICG@ZIF-8, which was capable of self-sufficient O₂ delivery and GSH depletion to enhance PDT and PTT synergistic therapy. We utilized ZIF-8 as nanocarriers that when loaded with CaO₂ and indocyanine green (ICG) form CaO₂/ICG@ZIF-8 nanoparticles, which exhibit a uniform particle size distribution and a hydrated particle size of about 215 nm. CaO₂ reacts with water under acidic conditions to produce O₂ so CaO₂/ICG@ZIF-8 has an excellent O₂ supply capacity, which is essential for PDT. Moreover, CaO₂/ICG@ZIF-8 also reacts with GSH to form glutathione disulfides (GSSH), enhancing the therapeutic outcome of PDT by preventing the consumption of local ractive oxygen species. Beyond that, CaO₂/ICG@ZIF-8 can produce strong hyperthermia with a photothermal conversion efficiency of about 44%, which is exceedingly appropriate for PTT. Owing to its augmentation, PTT/PDT mediated by CaO₂/ICG@ZIF-8 demonstrates intense tumor inhibitory effects in both in vitro and in vivo studies. Notably, the Zn and Ca generated by CaO₂/ICG@ZIF-8 degradation are essential elements for the body, so CaO₂/ICG@ZIF-8 shows favorable safety. Altogether, the research provides a promising PDT/PTT synergistic therapeutic strategy for cancer and may show more medical applications in the future.