Lactobionic acid-modified dendrimer-entrapped gold nanoparticles for targeted computed tomography imaging of human hepatocellular carcinoma.

Abstract

Development of novel nanomaterial-based contrast agents for targeted computed tomography (CT) imaging of tumors still remains a great challenge. Here we describe a novel approach to fabricating lactobionic acid (LA)-modified dendrimer-entrapped gold nanoparticles (LA-Au DENPs) for in vitro and in vivo targeted CT imaging of human hepatocellular carcinoma. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 pre-modified with fluorescein isothiocyanate and poly(ethylene glycol)-linked LA were employed as templates to form Au nanoparticles. The remaining dendrimer terminal amines were subjected to an acetylation reaction to form LA-Au DENPs. The prepared LA-Au DENPs were characterized via different methods. Our results reveal that the multifunctional Au DENPs with a Au core size of 2.7 nm have good stability under different pH (5-8) and temperature (4-50 °C) conditions and in different aqueous media, and are noncytotoxic to normal cells but cytotoxic to the targeted hepatocarcinoma cells in the given concentration range. In vitro flow cytometry data show that the LA-Au DENPs can be specifically uptaken by a model hepatocarcinoma cell line overexpressing asialoglycoprotein receptors through an active receptor-mediated targeting pathway. Importantly, the LA-Au DENPs can be used as a highly effective nanoprobe for specific CT imaging of hepatocarcinoma cells in vitro and the xenoplanted tumor model in vivo. The developed LA-Au DENPs with X-ray attenuation property greater than clinically employed iodine-based CT contrast agents hold a great promise to be used as a nanoprobe for targeted CT imaging of human hepatocellular carcinoma.

• Authors: Hui Liu, Han Wang, Yanhong Xu, Rui Guo, Shihui Wen, Yunpeng Huang, Weina Liu, Mingwu Shen, Jinglong Zhao, Guixiang Zhang, Xiangyang Shi
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 6 Issue 9 Pg. 6944-53 (May 14 2014) ISSN: 1944-8252 [Electronic] United States
• PMID: 24712914 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Dendrimers
• Gold

Topics

• Animals
• Carcinoma, Hepatocellular (diagnostic imaging, metabolism)
• Dendrimers (metabolism)
• Flow Cytometry
• Gold (chemistry)
• Heterografts
• Humans
• Liver Neoplasms (diagnostic imaging, metabolism)
• Metal Nanoparticles
• Mice
• Microscopy, Electron, Transmission
• Spectrophotometry, Ultraviolet
• Tomography, X-Ray Computed