title: Lactosylated Glycogen Nanoparticles for Targeting Prostate Cancer Cells.
abstract: Glyconanoparticles that exhibit multivalent binding to lectins are desirable for molecular recognition and therapeutic applications. Herein we explore the use of glycogen nanoparticles as a biosourced glycoscaffold for engineering multivalent glyconanoparticles. Glycogen nanoparticles, a naturally occurring highly branched polymer of glucose, was functionalized with lactose, achieved through copper(I)-catalyzed alkyne-azide cycloaddition chemistry, for targeted interaction with lectins ex situ and on prostate cancer cells. The lactosylated glycogen, which contains terminal β-galactoside moieties, is termed galacto-glycogen (GG), and is found to interact strongly with peanut agglutinin (PNA), a β-galactoside-specific lectin, as observed by optical waveguide lightmode spectroscopy, dynamic light scattering, and quartz crystal microbalance measurements. The GG nanoparticles exhibit multivalent binding to PNA with an affinity constant of 3.4 × 105M-1, and the GG-PNA complex cannot be displaced by lactose, demonstrating the competitive binding of GG to the lectin. These GG nanoparticles were tested for association with prostate cancer cell membranes in vitro, where the particles exhibited a high affinity for the membrane, as observed from flow cytometry and confocal microscopy. This is inferred to result from specific extracellular galectin-1 targeting. Furthermore, the GG nanoparticles induce aggregation between prostate cancer cells. Our results highlight a strategy for engineering a biosourced polysaccharide with surface moieties that exhibit strong multivalent interactions with lectins, and targeted interaction with prostate cancer cells.
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Quinn A
authors.initials: QA
authors.lastname: Besford
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wojnilowicz
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Tomoya
authors.identifier: http://orcid.org/0000-0002-3572-8988
authors.initials: T
authors.lastname: Suma
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bertleff-Zieschang
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.
authors.forename: Frank
authors.identifier: http://orcid.org/0000-0002-0197-497X
authors.initials: F
authors.lastname: Caruso
authors.affiliation: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, The University of Melbourne , Parkville, Victoria 3010, Australia.|Dipartimento di Scienze e Tecnologie Chimiche, Universita' degli Studi di Roma "Tor Vergata", via della ricerca scientifica 1 , 00173 Rome, Italy.
authors.forename: Francesca
authors.identifier: http://orcid.org/0000-0001-5391-5069
authors.initials: F
authors.lastname: Cavalieri
mesh_terms: D006003:Glycogen; D006801:Humans; D007785:Lactose; D037102:Lectins; D008297:Male; D053758:Nanoparticles; D011471:Prostatic Neoplasms
chemical_list: D037102:Lectins; D006003:Glycogen; D007785:Lactose
keywords: glycogen; lectins; nanoparticle; prostate cancer; targeting; β-galactoside