The aim of this study was to design a drug delivery system based on poly(N-isopropylacrylamide) (pNIPAM) nanoparticles (NPs). The model drug, Celecoxib, is a cyclooxygenase-2 inhibitor and has a great potential in chemoprevention and treatment of various cancer types, however, the clinical use is limited due to the side effects on the cardiovascular system which is most probably due to the high doses used in clinical applications. In this study, a novel nanoparticle preparation approach, nanoprecipitation, was used. The amount of crosslinker affected the size, encapsulation efficiency, loading and release rate of NPs. The antiproliferative effect of Celecoxib was tested on human osteosarcoma cells, Saos-2, and the nanoparticles were found to have cytotoxicity. Celecoxib loaded pNIPAM NPs had higher cytotoxicity and the cells treated with this formulation showed abnormal nuclear and cytoskeletal morphology indicating apoptosis. The nanoparticles were detected within the cytoplasm and their distribution differed depending on whether NP is loaded with Celecoxib or not. The drug delivery system developed in this study appears to have a potential as an antiproliferative tool in various applications such as prevention of restenosis or biofilm formation on biomaterials.