To investigate the anti-cancer activity of curcumin-loaded hydrogel nanoparticle derived aggregates on A549 lung adenocarcinoma cells. Curcumin was incorporated with biopolymeric chitosan, gelatin, and hyaluronan nanoparticles using an electrostatic field system. Characteristics of curcumin-loaded aggregates were examined including size and morphology, incorporation efficiency, stability and in vitro release. Treatment effect on A549 cells were assessed with cell viability assay, apoptosis assay, cell cycle analysis, reactive oxygen species detection, and Western blot. Observation from transmission electron microscopy show that the prepared biopolymeric nanoparticles were approximately 3-4 nm in diameter and that the size of the aggregates increased to approximately 26-55 nm after the incorporation of curcumin with the nanoparticles. The incorporation efficiency of curcumin into the chitosan, gelatin, and hyaluronan nanoparticles was 81, 67, and 78 % respectively. The formation of hyaluronan/curcumin and gelatin/curcumin aggregates seems to improve the stability of curcumin drug. The chitosan/curcumin aggregate has a faster release of curcumin than gelatin/curcumin and hyaluronan/curcumin aggregates. Treatment with chitosan/curcumin, gelatin/curcumin and hyaluronan/curcumin aggregates resulted in higher apoptosis rates of 45, 40 and 32 %, respectively, as compared to pure curcumin (less than 20 %) via Annexin V-FITC/PI analysis. Chitosan/curcumin aggregates induce the highest apoptosis effect (indicated by sub-G1 phase). In summary, chitosan/curcumin, gelatin/curcumin, and hyaluronan/curcumin aggregates represent higher anticancer proliferation properties in A549 cells than curcumin alone that exhibit great potential enhancement by either using fewer drugs or a decreased duration.