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Doxorubicin and paclitaxel co-bound lactosylated albumin nanoparticles having targetability to hepatocellular carcinoma

Title
Doxorubicin and paclitaxel co-bound lactosylated albumin nanoparticles having targetability to hepatocellular carcinoma
Author
최한곤
Keywords
Albumin nanoparticles; Lactose; Liver targetability; Hepatocellular carcinoma; Asialoglycoprotein receptor; Nab (R) Technology; DRUG-DELIVERY-SYSTEMS; SERUM-ALBUMIN; ASIALOGLYCOPROTEIN RECEPTOR; TARGETED DELIVERY; LUNG-CANCER; IN-VIVO; LIVER; CARRIER; IMPACT; TRAIL
Issue Date
2017-02
Publisher
ELSEVIER SCIENCE BV
Citation
COLLOIDS AND SURFACES B-BIOINTERFACES, v. 152, Page. 183-191
Abstract
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 naive BSA then characterized by mass spectrometry. Dox/Pac Lac-BSA NPs were fabricated utilizing high-pressure homogenization and evaporation with Nab (R) (nanoparticle albumin bound) technology. Dox/Pac Lac-BSA NPs were spherical and well-dispersed, with a 148.7 +/- 13.8 nm particle size and -54.1 +/- 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 mu g/ml) for Dox/Pac Lac-BSA NPs was 3.2 time lower than plain Dox/Pac BSA NPs (IC50; 0.68 +/- 0.04 mu g/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 (R) technique can be a potential therapeutic vector for treating HCC via hepatocyte targeting. (C) 2017 Elsevier B.V. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S0927776517300267http://repository.hanyang.ac.kr/handle/20.500.11754/71728
ISSN
0927-7765; 1873-4367
DOI
10.1016/j.colsurfb.2017.01.017
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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