Abstract: OBJECTIVE  To prepare pH-sensitive liposomes with arsenic trioxide and evaluate the anti-glioma activity in vitro and safety in vivo.METHODS  The hydrophobic modified MnAs coprecipitates were prepared by reverse phase microemulsion method, and liposomes loaded with MnAs coprecipitations (Liposome/MnAs) were prepared by emulsion evaporation method. The particle size, PDI and Zeta potential of Liposome/MnAs were measured. The morphology of Liposome/MnAs was observed by transmission electron microscopy. Encapsulation efficiency was determined by inductively coupled plasma mass spectrometer. Dialysis bag method was used to investigate the drug release characteristics under different pH conditions in vitro. The ability of in vitro MRI imaging was investigated under acidic conditions. The uptake and intracellular distribution of Liposome/C6 in mouse derived glioma cells GL261 were observed by confocal microscopy. The toxicity of free arsenic trioxide and Liposome/MnAs on GL261 was investigated by thiazolium blue assay. The apoptosis effect of free arsenic trioxide and Liposome/MnAs on GL261 cells was detected by flow cytometry. Liposomes were labeled with coumarin 6.RESULTS  The prepared MnAs coprecipitations were hydrophobic and could be dissolved by chloroform well. Liposome/MnAs were spherical in shape, with a particle size of (286.43±6.41) nm and As encapsulation efficiency of (48.32±5.95)%. It could quickly respond to release As³⁺ and Mn²⁺ under the condition of pH 5.4, and had a good ability of in vitro MRI imaging Cell uptake assay showed that GL261 cells had a good uptake of C6-labeled liposomes, which were mainly distributed in the cytoplasm. The inhibitory effect of Liposome/MnAs on GL261 cell growth was higher than that of free arsenic trioxide, and the IC₅₀ decreased from 4.74μmol/L to 2.99μmol/L. Apoptosis experiments also showed that Liposome/MnAs had a better effect on promoting the apoptosis of GL261 cells than free arsenic trioxide, and the proapoptotic rate was increased from 13.73% to 21.42%. Liposome/MnAs had no obvious toxicity to the main organs in mice within an administration cycle.CONCLUSION  The MnAs coprecipitates prepared by reverse microemulsion method have good hydrophobicity and can be encapsulated to by liposome prepare Liposome/MnAs, which had pH-responsive drug release characteristics, could enhance ATO uptaked by glioma cell GL261. The Liposome/MnAs enhanced the toxicity of arsenic trioxide to GL261 cell and had certain safety in vivo.