6-Thioguanine encapsulated chitosan nanoparticles (6-TG-CNPs) has formulated by the ionic-gelation method. Morphologically, the 6-TG-CNPs were spherical and showed mean size, PDI, zeta potential, and entrapment efficiency of 261.63 +/- 6.01 nm, 0.34 +/- 0.10, +15.97 +/- 0.46 mV and 44.27%, respectively. The IR spectra confirmed the 6-TG complex with chitosan. The in vitro drug release profile of 6-TG-CNPs revealed an increase in sustainedrelease (91.40 +/- 1.08% at 48 h) at pH 4.8 compared to less sustained-release (73.96 +/- 1.12% at 48 h) at pH 7.4. The MTT assay was conducted on MCF-7 and PA-i cell lines at 48 h incubation to determine % cell viability. The IC50 values of 6-TG, 6-TG-CNPs, and curcumin for MCF-7 were 23.09, 17.82, and 15.73 mu M, respectively. Likewise, IC50 values of 6-TG, 6-TG-CNPs, and curcumin for PA-1 were 5.81, 3.92, and 12.89 mu M, respectively. A combination of 6-TG-CNPs (lC(25)) with curcumin (lC(25)) on PA-1 and MCF-7 showed % cell viability of 43.67 +/- 0.02 and 49.77 +/- 0.05, respectively. The in vitro cytotoxicity potential in terms of% cell viability, early apoptosis, G2/M phase arrest, and DNA demethylating activity of 6-TG-CNPs alone and combination with curcumin proved to be more effective than that of 6-TG on PA-1 cells. (C) 2020 Elsevier B.V. All rights reserved.