A rapid and simple strategy is reported for the synthesis of amorphous calcium phosphate (ACP) vesicle-like nanospheres using the adenosine 5′-triphosphate (ATP) disodium salt as a biocompatible phosphorus source and stabilizer by the sonochemical method in mixed solvents of water and ethylene glycol (EG). The ACP vesicle-like nanospheres are characterized by X-ray powder diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, UV/Vis absorption spectroscopy, thermogravimetric (TG) analysis, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), dynamic light scattering (DLS) and Brunauer–Emmett–Teller (BET) nitrogen adsorption. The ACP vesicle-like nanospheres exhibit essentially inappreciable toxicity to the cells in vitro. Furthermore, the as-prepared ACP vesicle-like nanospheres can be used as anticancer drug nanocarriers and show a pH-responsive drug release behaviour using doxorubicin (Dox) as a model drug. The ACP vesicle-like nanosphere drug delivery system exhibits a high ability to damage cancer cells, thus, it is promising for application in pH-responsive drug delivery.