The biomaterial surface can be essentially upgraded with the therapeutic function by the introduction of controlled, local elution of biologically active molecules. The use of ultrasonicassisted formation of nanoparticles with controlled size and morphology can be readily utilized for such functionalization. In this study, the synthesis route for the generation of nanoparticles of fluorouracil, the bioactive molecule used in anticancer therapy, was reported. The tandem of experimental (TEM, NTA, ATR-IR) and computational (MD simulations) approaches allowed us to obtain a molecular-level picture of the cavitation bubble interface where the enrichment of fluorouracil molecules takes place. Thanks to the originally developed computational model of cavitation bubbles, we revealed that the bubble interface plays a key role in the prearrangement of drug and solvent molecules, initiating the formation of nanoparticles' seeds. The proposed mechanism can be applied to other biologically relevant molecules, suggesting that the sonochemical method can be used for the controlled formation of their nanoparticles. The results indicate a feasible way to tailor the surface of polymeric biomaterials via the embedment of nanoparticles, thus having the potential to be used for practical implications as drug delivery systems.