Effective targeting of hepatocellular carcinoma through glypican-3 ligand peptide functionalization of silica nanoparticles

Among the various nanosized particles developed for innovative biomedical applications, like selective molecular imaging and targeted drug delivery, silica nanoparticles (SiNPs) seem to be particularly attractive since of their low cost, low toxicity, ease of functionalization and acoustic properties. In fact, SiNPs have been demonstrated to effectively enhance ultrasound contrast at clinical diagnostic frequencies and, therefore, they might be potentially employed in non-ionizing echographic molecular imaging. Aim of this work was the development of a silica nanoparticle based system for in vitro molecular imaging of hepatocellular carcinoma, using both ultrasound and laser-scanning confocal microscopy, by exploiting the particular feature of these tumor cells to express on their surface high levels of Glypican-3 protein (GPC-3). At this regard, we have designed and characterized novel GPC-3 ligand peptide-functionalized fluorescent silica nanoparticles and tested them on GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. Laser scanning confocal microscopy analysis showed that GPC-3-targeted fuorescent SiNP, in the concentration range used for experimental ultrasound detection, did not exert significant cytotoxic effects and were effectively bound and taken up by HepG2 cells. These results suggest that silica nanoparticles might be a very promising contrast agents for non-ionizing ultrasound molecular imaging since of their high biocompatibility, targeting effectiveness and ultrasound enhancement power.