Highly mesoporus spherical three dimensional (3D) ZnO nanoassemblies have been fabricated by a simple, facile soft-chemical approach. It has been observed that the mesoporous (average pore diameter of 28 nm) nanoscale assembly comprised of numerous nanocrystals of average size 20 nm is fairly stable, well-defined and discrete, with a hexagonal wurtzite structure. The drug-loading efficiency of the nanoassemblies was investigated using doxorubicin hydrochloride (DOX) as a model drug to evaluate their potential as a carrier system. The quenching of the fluorescence intensity as well as the change in band positions and spectra shapes strongly suggest the interaction of drug molecules with ZnO. More specifically, the present investigation discusses a method for entrapping drugs at sites capable of complexing with transition metal ions and suggests that drug release is dependent on the pH of the medium and externally applied ultrasound (continuous or pulsatile), as well as the nature of the materials which encapsulate the drug. In addition, nanoassemblies are biocompatible with HeLa cells and do not have toxic effects for further in vivo use. Specifically, a new paradigm for precise control of targeted, on-demand drug delivery using ultrasound irradiation is demonstrated.