Synthesis and cellular uptake of scatteredly cyclic RGDfK-conjugated superparamagnetic iron oxide nanoparticles

We prepared scatteredly cyclic RGDfK-conjugated water-dispersible superparamagnetic iron oxide nanoparticles (cRGDfK–WSPIONs) and investigated their cellular uptake to MS-1 cells (mouse endothelial cell lines, express integrin αvβ3) and MCF-7 cells (human breast cancer cells, express low level of integrin αvβ3) using in vitro MRI. The cRGDfK–WSPIONs were prepared from oleate-protected SPIONs (SPION–OA) as follows. Some oleates (OAs) on the SPION–OA were substituted by mercaptohexadecanoic acids (MHA) and cRGDfKs were conjugated to MHAs. Finally, the remaining OAs were substituted by mercaptopropionic acids without detaching preexisting cRGDfK-conjugated MHA ligands from the SPION surface. The cRGDfK–WSPIONs showed drastically higher cellular uptake than its corresponding control WSPIONs to MS-1 cells and also, showed higher selectivity to MS-1 cells than to MCF-7 cells, both implicating integrin αvβ3-mediated cellular uptake of scatteredly cRGDfK-conjugated WSPIONs.