Nanoparticle surface chemistry is a fundamental engineering parameter that governs tumor-targeting activity. Electrostatic assembly generates controlled polyelectrolyte complexes through the process of adsorption and charge overcompensation utilizing synthetic polyions and natural biomacromolecules; it can yield films with distinctive hydration, charge and presentation of functional groups. Here, we used electrostatic layer-by-layer (LbL) assembly to screen ten different surface chemistries for their ability to preferentially target human ovarian cancer in vitro. Our screen identified that poly-L-aspartate, poly-L-glutamate, and hyaluronate-coated LbL nanoparticles have striking specificity for ovarian cancer, while sulfated poly(β-cyclodextrin) nanoparticles target noncancerous stromal cells. We validated top candidates for tumor-homing ability with a murine model of metastatic disease and with patient-derived ovarian cancer spheroids. Nanoparticle surface chemistry also influenced subcellular trafficking, indicating strategies to target the cell membrane, caveolae, and perinuclear vesicles. Our results confirm LbL is a powerful tool to systematically engineer nanoparticles and achieve specific targeting.
November 6, 2019
Use of GMI-1271, an E-selectin antagonist, in healthy subjects and in 2 patients with calf vein thrombosis.
March 2, 2020
Risk factors for avoidable hospitalizations in Canada using national linked data: A retrospective cohort study.
March 18, 2020