Abstract: Multimodal synergistic therapeutic nanomaterials exhibit significant research value for precision tumor therapy. However, the traditional preparation process is complex and the therapeutic efficacy of synergistic therapy remains suboptimal. In this study, an ultrasonically assisted self-assembly strategy is developed to synthesize iron-protoporphyrin IX (PpIX) coordination particle (Fe-PpIX). This approach achieves a three-in-one multimodal tumor therapy through photodynamic/sonodynamic/chemodynamic therapy. The prepared nanoparticles were characterized by TEM, XPS and FTIR, which indicated that Fe was successfully coordinated with PpIX by carboxyl groups. The quantitative evaluation of fluorescence spectroscopy demonstrated the efficient ROS generation of Fe-PpIX under photodynamic and sonodynamic conditions. The o-phenylenediamine/methylene blue dual probes further revealed that Fe-PpIX can catalyze the H2O2, which produce hydroxyl radicals by Fenton-like reaction. The MTT assays of L929 and 4T1 cells indicate that Fe-PpIX possesses good biocompatibility. After light/sound synergistic therapy, the survival rate of 4T1 tumor cells decreased significantly, and the survival rate decreased to the lowest (15.0%). This was further confirmed by live/dead cell staining experiments. The developed nanoparticles exhibit a valuable potential for achieving highly efficient therapy, providing a promising strategy for the rational design of multimodal therapeutic nanomaterials.

Key words: Self-assembly; Multimodal synergistic therapy, Protoporphyrin IX, Photodynamic, Sonodynamic