Modification of MR molecular imaging probes with cysteine-terminated peptides and their potential for in vivo tumour...

One of the challenges facing superparamagnetic iron oxide (SPIO) nanoparticles is to improve their biological compatibility. While highly uniform SPIOs can be manufactured, the surfaces are hydrophobic as a result of the surfactants used in their fabrication. In this study, we developed a general strategy to fabricate an MR molecular imaging probe in one step by replacing hydrophobic surfactants with small peptides terminated with cysteine. The hydrophobic SPIO surface was transformed into a hydrophilic one by exchanging surface oleic acids with the peptides RGD-Cys or RGD-PEG-Cys. After the RGD-Cys and RGD-PEG-Cys peptide exchange, both RGD-Cys-SPIO and RGD-PEG-Cys-SPIO specifically targeted α(v)β(3)-expressing cells (A549) in vitro, with RGD-Cys-SPIO achieving this more efficiently. Furthermore, MR imaging of A549 tumors receiving RGD-Cys-SPIO or RGD-PEG-Cys-SPIO demonstrated that both the targeted particles could reach and label the α(v)β(3)-expressing tumor, much more efficiently than the non-targeted particles (Cys-SPIO). Histology showed that the probes not only target the tumor neovasculature but also extravasate from vessels and address the tumor cells. Our study shows that directly replacing oleic acid with cysteine or cysteine-terminated small peptides is a general strategy to transforming the hydrophobic surface of SPIO into a hydrophilic one, as well as providing targeting ligands. Such SPIOs are of interest as MR molecular imaging probes to detect for cancer in vivo.