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Poly(lactide-co-glycolide)-cholesterol (PLGA-C)-based nanoparticles (NPs) were developed for the tumor-targeted delivery of curcumin (CUR). PLGA-C/CUR NPs with ˜200 nm mean diameter, narrow size distribution, and neutral zeta potential were fabricated by a modified emulsification-solvent evaporation method. The existence of cholesterol moiety in PLGA-C copolymer was confirmed by proton nuclear magnetic resonance (1H NMR) analysis. In vitro stability of developed NPs after 24 h incubation was confirmed in phosphate buffered saline (PBS) and serum media. Sustained (˜6 days) and pH-responsive drug release profiles from PLGA-C NPs were presented. Blank PLGA and PLGA-C NPs exhibited a negligible cytotoxicity in Hep-2 (human laryngeal carcinoma) cells in the tested concentration range. According to the results of flow cytometry and confocal laser scanning microscopy (CLSM) studies, PLGA-C NPs presented an improved cellular accumulation efficiency, compared to PLGA NPs, in Hep-2 cells. Enhanced in vivo tumor targetability of PLGA-C NPs, compared to PLGA NPs, in Hep-2 tumor-xenografted mouse model was also verified by a real-time near-infrared fluorescence (NIRF) imaging study. Developed PLGA-C NPs may be a candidate of efficient and biocompatible nanosystems for tumor-targeted drug delivery and cancer imaging.