Glioma is still hard to be treated due to their complex microenvironment.In this study,a gold nanoparticle-based delivery system was developed.The system,An-PEG-DOX-AuNPs,was loaded with doxorubicin(DOX)through hydrazone,an acid-responsive linker,and was functionalized with angiopep-2,a specific ligand of low density lipoprotein receptor-related protein-1(LRP1),which could mediate the system to penetrate blood brain barrier and target to glioma cells.The particle size of An-PEG-DOXAuNPs was 39.9 nm with a zeta potential of 19.3 mV,while the DOX loading capacity was 9.7%.In vitro,the release of DOX from DOX-AuNPs was pH-dependent.At lower pH values,especially 5.0 and 6.0,release of DOX was much quicker than that at pH 6.8 and 7.4.After coating with PEG,the acidresponsive release of DOX from PEG-DOX-AuNPs was almost the same as that from DOX-AuNPs.Cellular uptake study showed obviously higher intensity of intracellular An-PEG-DOX-AuNPs compared with PEG-DOX-AuNPs.In vivo,An-PEG-DOX-AuNPs could distribute into glioma at a higher intensity than that of PEG-DOX-AuNPs and free DOX.Correspondingly,glioma-bearing mice treated with An-PEG-DOX-AuNPs displayed the longest median survival time,which was 2.89-fold longer than that of saline.In conclusion,An-PEG-DOX-AuNPs could specifically deliver and release DOX in glioma and significantly expand the median survival time of glioma-bearing mice.