Abstract
As effective treatment of glioblastoma is still an unmet need, targeted delivery systems for efficient treatment are of utmost interest. Therefore, in this paper, surface modifications with a small peptide c(RGD) or physiological protein (ApoE3) were investigated. Cellular uptake in murine endothelial cells (bEnd.3) and different glioma cells (human U-87 MG, rat F98) was tested to elucidate possible differences and to correlate the uptake to the receptor expression. Different liposomal formulations were measured at 1 and 3 h for three lipid incubation concentrations. We calculated the liposomal uptake saturation S and the saturation half-time t1/2. An up to 9.6-fold increased uptake for ApoE3-modified liposomes, primarily in tumor cells, was found. Contrarily, c(RGD) liposomes showed a stronger increase in uptake in endothelial cells (up to 40.5-fold). The uptake of modified liposomes revealed enormous differences in S and t1/2 when comparing different tumor cell lines. However, for ApoE3-modified liposomes, we proved comparable saturation values (~25,000) for F98 cells and U-87 MG cells despite a 6-fold lower expression of LRP1 in F98 cells and a 5-fold slower uptake rate. Our findings suggest that cellular uptake of surface-modified liposomes depends more on the target structure than the ligand type, with significant differences between cell types of different origins.