In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles

Abstract Nucleolin (NCL) plays an important role in tumor vascular development. An increased endothelial expression level of NCL has been related to cancer aggressiveness and prognosis and has been detected clinically in advanced tumors. Here, with a peptide targeted to NCL (F3 peptide), we created an NCL-targeted microbubble (MB), and compared the performance of F3-conjugated MBs with non-targeted (NT) MBs both in vitro and in vivo . In an in vitro study, F3-conjugated MBs bound 433 times more than NT MBs to a NCL-expressing cell line, while pretreating cells with 0.5 mM free F3 peptide reduced the binding of F3-conjugated MBs by 84%, n = 4, p