Investigating the role of mucin in the delivery of nanoparticles to cellular models of human cancer disease: an in vitro study

Mucin, a glycosylated protein, is aberrantly overexpressed in a variety of tumor cells. The glycoprotein mesh decreases the rate of intracellular drug uptake and effectiveness. We investigated the influence of the mucin mesh on the cellular uptake of anti-MUC1 antibody and nanoparticles by fluorescence spectroscopy and microscopy. A glycosylation inhibitor (benzyl-α-GalNAc) was employed to regulate mucin glycosylation events. In our panel of pancreatic cell lines, only PANC-1 cells exhibited a significant increase in the uptake of liposomes following glycosylation inhibition, resulting in improved cytotoxicity of gemcitabine-loaded liposomes. Interestingly, areas devoid of liposome uptake were observed for pancreatic cancer cell lines PANC-1, Capan-1, and Capan-2; however, these restricted regions could be diminished for PANC1 cells only. In conclusion, investigating the reason(s) for differential cellular uptake of nanoparticles, in association with the production of mucin glycosylation mesh, should provide valuable leads to the future development of nanomedicine for cancer treatment.

Following the inhibition of mucin type-o-glycosylation of PANC-1 cells the cellular uptake of liposomes improved significantly. The effect was cell line-dependent. For example, this was not the case for human pancreatic cancer cell lines that express substantially greater levels of membrane-bound mucin (such as with the Capan-1 and Capan-2 cells), or for cells that lack the ability to produce mucin (such as human glioblastoma cells- U87-MG).Figure optionsDownload high-quality image (126 K)Download as PowerPoint slide