Herein, we report a new modified nanoprecipitation method for the fabrication of water-dispersible Poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating three poorly water-soluble anticancer agents as model drugs: paclitaxel (PTX), docetaxel (DTX) or curcumin (Cur). These nanoparticles were water dispersible with favourable size for anticancer applications (below 200 nm) and relatively high drug loading (6.3-8.9%). These nanoparticles were stable for four weeks in solid state and up to 48 h when dispersed in water. PTX and Cur nanoparticles showed a very minimal release of the payload during a 72-h in vitro release study. The new method also yielded reproducible results across three different batches of each type of nanoparticles and following three times upscaling of PTX nanoparticles. PTX and Cur nanoparticles were more effective than the free drugs against MDA-MB-231 cells (p < 0.05). In addition, PTX nanoparticles showed a significant enhanced induction of early apoptosis in MDA-MB-231 cells (42.3%) in comparison to free PTX (23.7%, p < 0.05). Both flow cytometry and confocal microscopy confirmed the uptake of the nanoparticles by MDA-MB-231 cells. In conclusion, our modified nanoprecipitation method produces PLGA nanoparticles loaded with different anticancer agents and suitable for cancer therapy.