Folate-mediated Cell Uptake of Shell-crosslinked Spheres and Cylinders

This paper reports the synthesis of shell crosslinked nanoparticles (SCKs) of spherical and cylindrical shapes, and their functionalization with folate using a poly(ethylene glycol) (PEG) construct that has folate and an amine group as the opposing chain termini. By use of confocal microscopy, we demonstrate the selective delivery of folate conjugated SCKs to human KB cells, a cell line that overexpresses the folate receptor (FR). A higher extent of polymer uptake by the cells occurred with the cylindrical SCK morphology, relative to the spherical SCKs, when both samples had the same fluorescein-5-thiosemicarbazide and polymer concentrations. In both cases, by using excess free folic acid as a block or SCKs lacking the folate-PEG conjugate, cell uptake was significantly reduced. These results suggest that particle shape may play an important role in receptor-mediated cell uptake, and may be exploited in the targeted delivery of nanoscopic drugs.