<p>Nanoclays such as Laponite are promising drug carriers due to their layered structure and biocompatibility; however, their performance is often limited by challenges such as clay aggregation, burst or uncontrolled drug release. To address these limitations, we synthesized an organic–inorganic hybrid by grafting (3-aminopropyl)triethoxysilane (APTES) onto Laponite, enhancing its capacity to load and control release of the anticancer drug 5-fluorouracil. Structural characterization by FTIR shows the presence of APTES functional groups, later confirmed to the covalently bound with Laponite using ²⁹Si MAS NMR. In addition, pXRD and SAXS reveal the interlayer increase, indicating the preference of the modification on the interlayer surface and the drug incorporation as well. Also, SEM revealed a morphology change from smooth pristine Laponite to a rougher hybrid surface, evidencing a reorganization of the layered framework and the formation of a hybrid material, instead of a functionalization. With TGA we estimate the amount of APTES incorporated to be around 19.2% the initial mass of Laponite, and N₂ adsorption reveals the decrease of the specific surface area from 359 to 202 m²·g⁻¹. The hybrid exhibited improved 5-FU loading (36%) compared to pristine Laponite (22%) and suggested a slower, diffusion-driven, pH-responsive release favoring acidic tumor-like environments. Biocompatibility assays indicated low cytotoxicity and reduced irritant potential upon drug incorporation. These findings suggest that the Laponite–APTES hybrid is a versatile platform for controlled, stimuli-responsive drug delivery, with potential applications in cancer therapy.</p> Graphical Abstract <p></p>