title: Development of quinic acid-conjugated nanoparticles as a drug carrier to solid tumors.
abstract: Nanometer-sized drug carriers including polymeric nanoparticles (NPs) have been used to increase biodistribution of a drug in tumors, thereby reducing the effective dose of chemotherapy. NPs increase drug delivery to tumors to a certain extent, but the amount reaching tumors is only a small fraction of the total administered NPs because they depend on passive accumulation via the leaky vasculature surrounding tumors. In an attempt to further increase the drug delivery to tumors, we develop a polymeric NP system that interacts with an endothelial tumor marker. The NPs are decorated with quinic acid, a synthetic mimic of sialyl Lewis-x, which binds to E-selectin, overexpressed on the surface of endothelial cells surrounding solid tumors. The NPs selectively bind to endothelial cells activated with tumor necrosis factor-α, with weak affinity at a relatively high shear stress. These properties may help NPs reach tumors by increasing the encounter of NPs with the peritumoral endothelium without hindering subsequent transport of the NPs.
authors.affiliation: Department of Industrial and Physical Pharmacy, Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Zohreh
authors.initials: Z
authors.lastname: Amoozgar
authors.forename: Joonyoung
authors.initials: J
authors.lastname: Park
authors.forename: Qingnuo
authors.initials: Q
authors.lastname: Lin
authors.forename: Johann H
authors.initials: JH
authors.lastname: Weidle
authors.forename: Yoon
authors.initials: Y
authors.lastname: Yeo
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D019040:E-Selectin / Q000737:chemistry; D018922:HL-60 Cells; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy*; D011801:Quinic Acid / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D019040:E-Selectin; D011801:Quinic Acid