Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles

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.
Tumor microenvironment Sensitive release Doxorubicin Glioma Gold nanoparticles
Shaobo Ruan Mingqing Yuan Li Zhang Guanlian Hu Jiantao Chen Xingli Cun Qianyu Zhang Yuting Yang Qin He Huile Gao
Key Laboratory of Drug Targeting and Drug Delivery Systems,West China School of Pharmacy,and State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China
国内会议
成都
英文
425-435
2015-05-01(万方平台首次上网日期,不代表论文的发表时间)