title: Investigating the role of mucin in the delivery of nanoparticles to cellular models of human cancer disease: an in vitro study.
abstract: 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.
authors.affiliation: Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, School of Pharmacy, Department of Pharmaceutical Sciences, Worcester, MA, USA.
authors.forename: Musaed
authors.initials: M
authors.lastname: Alkholief
authors.affiliation: Massachusetts College of Pharmacy and Health Sciences (MCPHS) University, School of Pharmacy, Department of Pharmaceutical Sciences, Worcester, MA, USA. Electronic address: robert.campbell@mcphs.edu.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Campbell
mesh_terms: D000951:Antigens, Neoplasm / Q000008:administration & dosage; D006801:Humans; D018396:Mucin-1; D009077:Mucins / Q000502:physiology*; D053758:Nanoparticles; D010190:Pancreatic Neoplasms / Q000188:drug therapy*
chemical_list: D000951:Antigens, Neoplasm; D018396:Mucin-1; D009077:Mucins
keywords: Cancer; Drug delivery; Glycosylation; Liposomes; Microspheres; Mucin; Nanotechnology; Pancreatic cancer; Tumor barriers