Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery

摘要

Uptake of cytotoxic drugs by typical tumor cells is limited by the dense dendritic network ofnoligosaccharide mucin chains that forms a mechanical barrier. Atomic force microscopy is used tondirectly measure the force needed to pierce the mucin layer to reach the cell surface. Measurementsnare analyzed by de Gennes’ steric reptation theory. Multidrug resistant ovarian tumor cells showsnsignificantly larger penetration load compared to the wide type. A pool of pancreatic, lung,ncolorectal, and breast cells are also characterized. The chemotherapeutic agent, benzyl-u0002-GalNac,nfor inhibiting glycosylation is shown to be effective in reducing the mechanical barrier. © 2010nAmerican Institute of Physics. u0004doi:10.1063/1.3532847