Journal
POLYMER CHEMISTRY
Volume 7, Issue 3, Pages 715-721Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/c5py01625h
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Funding
- National Natural Science Foundation of China [21274004]
- China Postdoctoral Science Foundation [2015M570880]
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A GSH sensitive nanocarrier (G4-DOX-Angiopep-PEG), with Angiopep-2 as a dual-targeting group and doxorubicin (DOX) as the therapy drug, was constructed by covalently conjugating them on the periphery of fourth generation PAMAM dendrimers (G4 PAMAM), aiming for an enhancement of BBB transportation and drug accumulation in glioma cells. It was found that the DOX release reached 44% with the concentration of GSH at 10 mM in the system, while only 3% DOX was released at pH 7.4 without GSH. The in vitro assay of transport across the BBB model showed that G4-DOX-Angiopep-PEG delivered 11% of DOX in a period of 12 h. The carrier could internalize into C6 glioma cells through low-density lipoprotein receptor-related protein (LRP)-mediated transcytosis. The accumulation of DOX in the tumor site was increased due to the targeting effects of Angiopep-2 via LRP-mediated endocytosis, which resulted in the volume of the avascular C6 glioma spheroids being effectively reduced in vitro.
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