A dual-targeting nanocarrier based on poly(amidoamine) dendrimers conjugated with transferrin and tamoxifen for treating brain gliomas

作者: Yan Li , Hai He , Xinru Jia , Wan-Liang Lu , Jinning Lou

DOI: 10.1016/J.BIOMATERIALS.2012.02.004

关键词: TransferrinPoly(amidoamine)EndocytosisDrug carrierBiophysicsCellular pathologyNanocarriersDendrimerChemistryBiochemistryGlioma

摘要: Abstract A pH-sensitive dual-targeting drug carrier (G4-DOX-PEG-Tf-TAM) was synthesized with transferrin (Tf) conjugated on the exterior and Tamoxifen (TAM) in interior of fourth generation PAMAM dendrimers for enhancing blood–brain barrier (BBB) transportation improving accumulation glioma cells. It found that, average, 7 doxorubicine (DOX) molecules, over 30 PEG1000 PEG2000 chains one Tf group were bonded periphery each G4 dendrimer, while 29 TAM molecules encapsulated into per dendrimer. The pH-triggered DOX release 32% at pH 4.5 6% 7.4, indicating a comparatively fast weak acidic condition stable state physiological environment. in vitro assay transport across BBB model showed that G4-DOX-PEG-Tf-TAM exhibited higher ability transporting ratio 6.06% 3 h. internalized C6 cells upon crossing by coactions TfR-mediated endocytosis inhibition effect to efflux transports. Moreover, it also displayed avascular spheroids made tumor volume effectively reduced.

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