Objective To prepare ultrasound responsive nanoparticles (NP) TPZ-GOD NP with zinc porphyrin (TPZ), glucose oxidase (GOD) and perfluoropentane, also to evaluate the effect of ultrasound/photoacoustic imaging and mediating sonodynamic therapy (SDT)/starvation therapy for colorectal cancer in mice. Methods Ultrasound responsive NP were synthesised by using a film hydration method with TPZ and GOD. The properties of TPZ-GOD NP were assessed, and the release amount of GOD assisted by ultrasound irradiation was evaluated. The intracellular uptake of CT-26 cells co-incubated with TPZ-GOD NP were studied with flow cytometry after various intervals of incubation. The cytotoxic reactive oxygen species generation of TPZ-GOD NP after ultrasound stimulation were observed under fluorescence microscope. Both in vitro and in vivo enhanced ultrasound/photoacoustic imaging performances were detected as well. The effects of SDT, starvation and the combined therapy for xenotransplant model mice were observed with ultrasound/photoacoustic imaging under the guidance of TPZ-GOD NP. Results TPZ-GOD NP were successfully fabricated, showing homogenized size distribution, the average particle size was (262.10±62.92)nm. Upon ultrasound irradiation, the release of GOD increased with time. TPZ-GOD NP could be phagocytized by CT-26 cells, and a large number of cytotoxic reactive oxygen species could be produced after ultrasonic irradiation. Liquid-gas phase transition occurred to enhance the effect of contrast-enhanced ultrasound in vivo and in vitro. In vitro photoacoustic imaging showed that the photoacoustic signals of TPZ-GOD NP increased linearly with the increase of concentration. After injection of TPZ-GOD NP into the tail vein of mice, the photoacoustic signals of tumor area remarkably enhanced. CT-26 cells were killed after the treatment of SDT or starvation therapy alone, while the killing effect of the combined therapy was better than of single ones. Conclusion The successfully prepared ultrasound responsive TPZ-GOD NP could be used for combined therapy (SDT/starvation therapy) for colorectal cancer in mice under the guidance of ultrasound/photoacoustic imaging.