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Issue 20, 2015
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A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

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Abstract

A safe and efficient liver targeted PEGylated liposome (PEG-Lip) based on N-terminal myristoylated preS1/21-47 (preS1/21-47myr) of hepatitis B virus was successfully developed. The study aimed to elucidate the cellular uptake mechanism of preS1/21-47myr modified PEG-Lip (preS1/21-47myr-PEG-Lip) in hepatogenic cells and the distribution behavior of preS1/21-47myr-PEG-Lip in Vr:CD1 (ICR) mice. The cellular uptake results showed that preS1/21-47myr-PEG-Lip was effectively taken up by hepatogenic cells (including primary hepatocytes and liver tumor cells) through a receptor-mediated endocytosis pathway compared with non-hepatogenic cells. After systemic administration to H22 hepatoma-bearing mice, preS1/21-47myr-PEG-Lip showed significant liver-specific delivery and an increase in the distribution of preS1/21-47myr-PEG-Lip in hepatic tumor. Furthermore, the antitumor effect of preS1/21-47myr-PEG-Lip loaded with paclitaxel (PTX) was remarkably stronger than that of PTX injection and PTX loaded liposomes (including common liposomes and PEG-Lip). In safety evaluation, no acute systemic toxicity and immunotoxicity were observed after intravenous injection of preS1/21-47myr-PEG-Lip. No liver toxicity was observed despite the dramatic increase of preS1/21-47myr-PEG-Lip in liver. Taken together, preS1/21-47myr-PEG-Lip represents a promising carrier system for targeted liver disease therapy and imaging.

Graphical abstract: A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

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Article information


Submitted
17 Aug 2014
Accepted
20 Apr 2015
First published
24 Apr 2015

Nanoscale, 2015,7, 9298-9310
Article type
Paper
Author version available

A safe and efficient hepatocyte-selective carrier system based on myristoylated preS1/21-47 domain of hepatitis B virus

Q. Zhang, X. Zhang, T. Chen, X. Wang, Y. Fu, Y. Jin, X. Sun, T. Gong and Z. Zhang, Nanoscale, 2015, 7, 9298
DOI: 10.1039/C4NR04730C

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