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 α(v)β(3)) and MCF-7 cells (human breast cancer cells, express low level of integrin α(v)β(3)) 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 α(v)β(3)-mediated cellular uptake of scatteredly cRGDfK-conjugated WSPIONs.