کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4983162 | 1454252 | 2017 | 9 صفحه PDF | دانلود رایگان |
Anticancer drug targeting to liver asialoglycoprotein receptors (ASGPR) is viewed as a good approach for hepatocellular carcinoma (HCC) treatment. Lactose residue is a promising ASGPR ligand due to its high receptor affinity. Herein, we introduce doxorubicin and paclitaxel co-bound lactosylated albumin (Lac-BSA) nanoparticles (Dox/Pac Lac-BSA NPs) with good liver targetability. Lac-BSA was synthesized by conjugating lactobionic acid to naïve BSA then characterized by mass spectrometry. Dox/Pac Lac-BSA NPs were fabricated utilizing high-pressure homogenization and evaporation with Nab® (nanoparticle albumin bound) technology. Dox/Pac Lac-BSA NPs were spherical and well-dispersed, with a 148.7 ± 13.8 nm particle size and â54.1 ± 0.7 mV zeta potential at a 100% Lac-BSA feed ratio. Combined Dox and Pac synergistic cytotoxicity was confirmed in Hep G2 cells. Specifically, the inhibitory concentration (IC50; 0.21 ± 0.02 μg/ml) for Dox/Pac Lac-BSA NPs was 3.2 time lower than plain Dox/Pac BSA NPs (IC50; 0.68 ± 0.04 μg/ml). Also, Dox/Pac Lac-BSA NPs exhibited better internalizing in Hep G2 cells (61.8% vs. 14.4% for Dox) and spheroids compared to Dox/Pac BSA NPs. Finally, Dox/Pac Lac-BSA NPs displayed much greater localization into ICR mice livers compared to Dox/Pac BSA NPs. This was indicated by the presence of NP lactose residues revealed by a galactose inhibition study. Based on these results, we suggest that lactose-modified albumin-based nanoparticles fabricated with the Nab® technique can be a potential therapeutic vector for treating HCC via hepatocyte targeting.
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Journal: Colloids and Surfaces B: Biointerfaces - Volume 152, 1 April 2017, Pages 183-191