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The nanoparticles exhibited sustained Ce6 release profiles with 50% released at the end of 3 days, whereas\n free Ce6 showed rapid release within 1 day. Ce6 release patterns were controlled by encapsulation into PLGA. The uptake of PLGA-Ce6 NPs was significantly enhanced by endocytosis in the first 8 hours in the HCT-116 cell line. An intracellular reactive oxygen species assay revealed the enhanced\n uptake of the nanoparticles. An <jats:italic>in vitro<\/jats:italic> anti-tumor activity assay showed that the PLGA-Ce6 NPs exhibited enhanced phototoxicity toward HCT-116 cells and a slightly lower IC<jats:sub>50<\/jats:sub> value in HCT-116 cells than Ce6 solution alone. Exposure of HCT-116 cell spheroids to PLGA-Ce6 NPs\n penetrated more profoundly and had better phototoxicity than pure drugs. 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