Photodynamic therapy (PDT) is a minimally invasive treatment strategy that uses photosensitizers and light in combination with oxygen to generate cytotoxic singlet oxygen (O-1(2)) to kill cancer cells by necrosis or apoptosis. However, the treatment effects are still not satisfactory because of the tumor hypoxia and the PDT-induced oxygen consumption. Here, we have successfully synthesized dendritic mesoporous organosilica nanoparticles (MONs) with large center-radial pore structure that can be used to simultaneously encapsulate indocyanine green (ICG, <1 nm) and macromolecule catalase (CAT, 2.0 nm x 6.0 nm x 9.0 nm) to overcome the tumor hypoxia. Upon 808 nm laser irradiation, ICG as the organic NIR dye can generate highly cytotoxic singlet oxygen (O-1(2)) and other reactive oxygen species (ROS) to kill cancer cells and realize photoacoustic (PA) imaging. The catalase can decompose the endogenous H2O2 in malignant cancerous cells into O-2 bubble to simultaneously intensify the ultrasound (US) imaging signal and enhance PDT efficacy. These results indicate that the ICG-CAT@MONs holds great promise in multimodal photoacoustic / ultrasound image-guided tumor PDT therapy. (C) 2020 Elsevier Inc. All rights reserved.