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Abstract In this paper, a type of phycocyanin (PC)-functionalized and curcumin (CUR)-loaded biotin-chitosan oligosaccharide-dithiodipropionic acid-curcumin (BCSC) nanoparticles, called CUR-BCSC@PCs, were designed to enhance the biocompatibility of CUR. The structure of BCSC was confirmed using 1H-NMR. In CUR-BCSC@PCs with an average hydrodynamic diameter of 160.3 ± 9.0 nm, the biomimetic protein corona gave the nanoparticles excellent stability and the potential to avoid protein adsorption in blood circulation. The in vitro release experiment verified that CUR-BCSC@PCs with redox responsive shells were sensitive to high concentrations of glutathione. In addition, CUR-BCSC@PCs were effective at increasing the inhibitory activity on the proliferation of A549 cells by enhancing the intracellular uptake of CUR. These results indicated that CUR-BCSC@PCs have great application prospects in cancer therapy as effective drug delivery carriers.