Fe₃O₄@TiO₂ Microspheres: Harnessing O₂ Release and ROS Generation for Combination CDT/PDT/PTT/Chemotherapy in Tumours

In the treatment of various cancers, photodynamic therapy (PDT) has been extensively studied as an effective therapeutic modality. As a potential alternative to conventional chemotherapy, PDT has been limited due to the low Reactive Oxygen Species (ROS) yield of photosensitisers. Herein, a nanoplatform containing mesoporous Fe₃O₄@TiO₂ microspheres was developed for near-infrared (NIR)-light-enhanced chemodynamical therapy (CDT) and PDT. Titanium dioxide (TiO₂) has been shown to be a very effective PDT agent; however, the hypoxic tumour microenvironment partly affects its in vivo PDT efficacy. A peroxidase-like enzyme, Fe₃O₄, catalyses the decomposition of H₂O₂ in the cytoplasm to produce O₂, helping overcome tumour hypoxia and increase ROS production in response to PDT. Moreover, Fe²⁺ in Fe₃O₄ could catalyse H₂O₂ decomposition to produce cytotoxic hydroxyl radicals within tumour cells, which would result in tumour CDT. The photonic hyperthermia of Fe₃O₄@TiO₂ could not only directly damage the tumour but also improve the efficiency of CDT from Fe₃O₄. Cancer-killing effectiveness has been maximised by successfully loading the chemotherapeutic drug DOX, which can be released efficiently using NIR excitation and slight acidification. Moreover, the nanoplatform has high saturation magnetisation (20 emu/g), making it suitable for magnetic targeting. The in vitro results show that the Fe₃O₄@TiO₂/DOX nanoplatforms exhibited good biocompatibility as well as synergetic effects against tumours in combination with CDT/PDT/PTT/chemotherapy.