Targeted uptake of folic acid-functionalized iron oxide nanoparticles by ovarian cancer cells in the presence but not in the absence of serum

Abstract

Targeted delivery of nanoparticles to cells or tissues of interest is arguably the "holy grail" of nanomedicine. Using primary human macrophages and ovarian cancer cells, we evaluated the biocompatibility and specific targeting of folic acid (FA)-conjugated iron oxide nanoparticles with organic [poly(ethylene glycol), PEG] or inorganic (SiO2) intermediate surface coatings. Reduction of folate receptor-α expression using specific siRNA resulted in a significant decrease in cellular uptake of the SiO2-coated nanoparticles, but did not affect uptake of PEG-coated nanoparticles. Notably, specific (i.e. FA-dependent) uptake was observed only in the presence of serum proteins. The strategy presented here for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable targeting of nanoparticles for therapeutic and imaging applications. From the clinical editor: In this study the receptor specific uptake of folic acid-functionalized iron oxide nanoparticles was determined in ovarian cancer cells. It was found that the presence of serum proteins is an absolute requirement for the uptake of these nanoparticles. The described strategy for receptor-mediated uptake of nanoparticles with pre-defined surface chemistry may enable a better targeting of nanoparticles for additional therapeutic and imaging applications.

Keywords: Biocompatibility; Folate receptor; Ovarian cancer; Superparamagnetic nanoparticles; Targeting.