Trials in developing a nanoscale material for extravascular contrast-enhanced ultrasound targeting hepatocellular carcinoma

BACKGROUND: Medical imaging is an important approach for the diagnosis of hepatocellular carcinoma (HCC), a common life threaten disease, however, the diagnostic efficiency is still not optimal. Developing a novel method to improve diagnosis is necessary. The aim of this project was to formulate a material that can combine with GPC3 of HCC for targeted enhanced ultrasound. METHODS: A material of sulfur hexafluoride (SF(6)) filled liposome microbubbles and conjugated with synthesized peptide (LSPMbs) was prepared and assessed in vitro and vivo. Liposome microbubbles were made of DPPC, DPPG, DSPE-PEG2000,and SF(6), using thin film method to form shell, followed filling SF(6), and conjugating peptide. A carbodiimide method was used for covalent conjugation of peptide to LSMbs. RESULTS: The prepared LSPMbs appeared round shaped, with size of 380.9 ± 176.5 nm, and Zeta potential of −51.4 ± 10.4mV. LSPMbs showed high affinity to Huh-7 cells in vitro, presented good enhanced ultrasound effects, did not show cytotoxicity, and did not exhibit targeted fluorescence and enhanced ultrasound in animal xenograft tumors. CONCLUSION: Extravascular contrast-enhanced ultrasound targeted GPC3 on HCC may not be realized, and the reason may be that targeted contrast agents of microbubbles are hard to access and accumulate in the tumor stroma and matrix.