TY - JOUR
T1 - Tumor microenvironment sensitive doxorubicin delivery and release to glioma using angiopep-2 decorated gold nanoparticles
AU - Ruan, Shaobo
AU - Yuan, Mingqing
AU - Zhang, Li
AU - Hu, Guanlian
AU - Chen, Jiantao
AU - Cun, Xingli
AU - Zhang, Qianyu
AU - Yang, Yuting
AU - He, Qin
AU - Gao, Huile
N1 - Publisher Copyright:
© 2014 Elsevier Ltd.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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-DOX-AuNPs was 39.9nm with a zeta potential of-19.3mV, while the DOX loading capacity was 9.7%. Invitro, 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 acid-responsive 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. Invivo, 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.
AB - 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-DOX-AuNPs was 39.9nm with a zeta potential of-19.3mV, while the DOX loading capacity was 9.7%. Invitro, 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 acid-responsive 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. Invivo, 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.
KW - Doxorubicin
KW - Glioma
KW - Gold nanoparticles
KW - Sensitive release
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84922324826&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2014.10.007
DO - 10.1016/j.biomaterials.2014.10.007
M3 - Article
C2 - 25453970
AN - SCOPUS:84922324826
SN - 0142-9612
VL - 37
SP - 425
EP - 435
JO - Biomaterials
JF - Biomaterials
ER -