Abstract: AimTo study the cellular uptake of chitosan oligosaccharide nanoparticles by A549 cells and evaluate the possibility of chitosan oligosaccharide nanoparticles used as a potential drug carrier. MethodsChitosan oligosaccharide (CSO) was obtained by ultrafiltration separation after regulation of the condition of chitosanase degradation. The molecular weight of CSO was determined by gel permeation chromatography (GPC). Chitosan oligosaccharide nanoparticles (CSO-NPs) were prepared by a novel solvent diffusion method in an oil system after the carrier material grafted fluorescein isothiocyanate (FITC) and the particle size distribution and zeta potential were determined by light scattering and electrophoretic mobility. The cytotoxicity and uptake of FITC-labeled CSO-NPs in A549 cells following various incubation periods were studied by the MTT method and fluorescence microscopy, flow cytometric analysis, respectively. ResultsThe molecular weight (_w) of CSO was 18 678 u and the particles sizes of CSO-NPs were 133.3 nm (number average) and 368.2 nm (volume average), respectively. The IC₅₀ of CSO and CSO-NPs were 944.36 and 643.16 mg·L^-1, respectively, and the result showed low cytotoxicity. Cellular uptake of CSO and CSO-NPs were relative to the concentration and the incubation time. Internalization of CSO-NPs increased 0.49-13.9 times more than that of the CSO with the same incubation time. ConclusionCSO and CSO-NPs have low cytotoxicity. CSO-NPs can significantly improved the uptake of CSO-NPs by A549 cells compared to the same molecular weight of CSO.