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

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2017-04, Vol.152, p.183-191
• Main Authors: Thao, Le Quang, Lee, Changkyu, Kim, Bomi, Lee, Sungin, Kim, Tae Hwan, Kim, Jong Oh, Lee, Eun Seong, Oh, Kyung Taek, Choi, Han-Gon, Yoo, Sun Dong, Youn, Yu Seok
• Format: Article
• Language: English
• Subjects: Albumin nanoparticles; Animals; Asialoglycoprotein receptor; Carcinoma, Hepatocellular - metabolism; Doxorubicin - chemistry; Doxorubicin - pharmacokinetics; Hep G2 Cells; Hepatocellular carcinoma; Humans; Lactose; Lactose - chemistry; Liver - metabolism; Liver Neoplasms - metabolism; Liver targetability; Mice; Mice, Inbred ICR; Nab® Technology; Nanoparticles - chemistry; Paclitaxel - chemistry; Paclitaxel - pharmacokinetics; Serum Albumin - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2017.01.017

[Display omitted] 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±13.8nm particle size and −54.1±0.7mV 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±0.02μg/ml) for Dox/Pac Lac-BSA NPs was 3.2 time lower than plain Dox/Pac BSA NPs (IC50; 0.68±0.04μg/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.