Abstract: Abstract: Objective To synthesize a new kind of acid-sensitive doxorubicin prodrug nanoparticles and to evaluate its anti-brain glioma effect and efficiency through blood-brain barrier (BBB). Methods The prodrug acid-sensitive poly⁃ ethylene glycol (PEG) - doxorubicin (PEG-DOX) copolymer was synthesized by Schiff base reaction, and PEG-DOX pro⁃ drug nanoparticles (PEG-DOX NPs) were prepared by self-assembling. The character of PEG-DOX copolymer was detected by dynamic light scattering (DLS) instrument and 1 H NMR. The morphology of PEG-DOX NPs was observed by transmission electron microscopy (TEM). The character of drug release was detected by UV mothed. The cellular uptake efficiency of glio⁃ ma cells to PEG-DOX NPs was observed by inverted fluorescence microscope. The anti-brain glioma effects of PEG-DOX NPs and Free DOX were studied by MTT mothed. PS80-PEG-DOX NPs were gained by the modification of PEG-DOX NPs with Tween 80. Nine BALB/c mice were separated into Free DOX, PEG-DOX NPs and PS80-PEG-DOX NPs groups by ran⁃ dom drawing lots. The mean fluorescence intensity of brain and main organs were observed by in vivo imaging system. Re⁃ sults The copolymer of PEG-DOX can self-assemble into nanoparticles with the diameter of 100 nm. PEG-DOX NPs can quickly release DOX in acid environment. Although PEG-DOX NPs had slow cancer cell uptake than Free DOX, it had lon⁃ger accumulation. MTT results showed that PEG-DOX NPs had concentration dependent anti-brain glioma effect. Indepen⁃ dent samples t-test indicated that the efficiency through BBB was significantly higher in PS80-PEG-DOX NPs group than that of Free DOX group and PEG-DOX NPs group. Conclusion PEG-DOX NPs show well anti-brain glioma effect in vi⁃ tro, and can across BBB with high efficiency after modification, which make it possible for a potential therapeutic prodrug for brain glioma.

Key words: blood-brain barrier, doxorubicin prodrug, nanoparticle, brain glioma, acid-sensitive