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Currently, how to effectively deliver drugs into tumor cells remains the major challenge for anti-cancer chemotherapy.In the present study, pH-sensitive dextran-retinal (Dex-RAL) nanoparticle was prepared as a drug delivery system.The morphology and physicochemical properties of Dex-RAL nanoparticle, such as particle size, zeta potential, and pH sensitivity were investigated.The result showed that the doxorubicin (DOX)-loaded Dex-RAL nanoparticles (DOX-Dex-RAL) demonstrated the hydrodynamic size about 120 nm with the zeta potential about + 0.45 mV.The release profile showed that the release of DOX in pH 5.0 phosphate buffer was much faster than that in pH 7.4 phosphate buffer.The confocal imaging showed that DOX-Dex-RAL nanoparticles were effectively internalized by MCF-7 breast cancer cells.After 2-4 h incubation, the encapsulated DOX were released into the cytosol and then translocalized into nuclei.The cytotoxic effect of DOX-Dex-RAL nanoparticles was investigated in several tumor cell lines using MTT assays.The results revealed that the IC50 (half inhibitory concentration) values of the free DOX was 0.1 μg/mL at 48 h.On the other hand, the ICs0 of DOX-Dex-RAL nanoparticles was 0.21 μg DOX equiv/mL, indicating similar cytotoxic effect as compared with free DOX.Hence, the DOX-loaded Dex-RAL nanoparticles could be a promising strategy for cancer chemotherapy.