Silica nanoparticles (SiNPs) are widely studied nanomaterials for their potential employment in advanced biomedical applications, such as selective molecular imaging and targeted drug delivery. SiNPs are generally low cost and highly biocompatible, can be easily functionalized with a wide variety of functional ligands, and have been demonstrated to be effective in enhancing ultrasound contrast at clinical diagnostic frequencies. Therefore, SiNPs might be used as contrast agents in echographic imaging. In this work, we have developed a SiNPs-based system for the in vitro molecular imaging of hepatocellular carcinoma cells that express high levels of glypican-3 protein (GPC-3) on their surface. In this regard, a novel GPC-3 targeting peptide was designed and conjugated to fluorescent silica nanoparticles. The physicochemical properties, acoustic behavior, and biocompatibility profile of the functionalized SiNPs were characterized; then binding and uptake of both naked and functionalized SiNPs were analyzed by laser scanning confocal microscopy and transmission electron microscopy in GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. The results obtained showed that GPC-3-functionalized fluorescent SiNPs significantly enhanced the ultrasound contrast and were effectively bound and taken up by HepG2 cells without affecting their viability.

Human Hepatocarcinoma Cell Targeting by Glypican-3 Ligand Peptide Functionalized Silica Nanoparticles: Implications for Ultrasound Molecular Imaging

QUARTA, ALESSANDRA;CONVERSANO, Francesco;BETTINI, SIMONA;VALLI, Ludovico;GIGLI, Giuseppe;
2017-01-01

Abstract

Silica nanoparticles (SiNPs) are widely studied nanomaterials for their potential employment in advanced biomedical applications, such as selective molecular imaging and targeted drug delivery. SiNPs are generally low cost and highly biocompatible, can be easily functionalized with a wide variety of functional ligands, and have been demonstrated to be effective in enhancing ultrasound contrast at clinical diagnostic frequencies. Therefore, SiNPs might be used as contrast agents in echographic imaging. In this work, we have developed a SiNPs-based system for the in vitro molecular imaging of hepatocellular carcinoma cells that express high levels of glypican-3 protein (GPC-3) on their surface. In this regard, a novel GPC-3 targeting peptide was designed and conjugated to fluorescent silica nanoparticles. The physicochemical properties, acoustic behavior, and biocompatibility profile of the functionalized SiNPs were characterized; then binding and uptake of both naked and functionalized SiNPs were analyzed by laser scanning confocal microscopy and transmission electron microscopy in GPC-3 positive HepG2 cells, a human hepatocarcinoma cell line. The results obtained showed that GPC-3-functionalized fluorescent SiNPs significantly enhanced the ultrasound contrast and were effectively bound and taken up by HepG2 cells without affecting their viability.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11587/411229
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