The synthesis of nanosized metal-organic frameworks (NMOFs) is requisite for their application as injectable drug delivery systems (DDSs) and other biorelevant purposes. Herein, we have critically examined the role of different synthetic parameters leading to the production of UiO-66 crystals smaller than 100 nm. Of note, we demonstrate the co-modulator role conferred by halide ions, not only to produce NMOFs with precise morphology and size, but also to significantly improve the reaction yield. The resulting NMOFs are highly crystalline and exhibit sustained colloidal stability in different biologically relevant media. As a proof of concept, these NMOFs were loaded with Rhodamine 6G (R6G), which remained trapped in most common biologically relevant media. When incubated with living mammalian cells, the R6G-loaded NMOFs were efficiently internalized and did not impair cell viability even at relatively high doses.