Targeting of a magnetic bionanomaterial to HepG2 human hepatocellular carcinoma cells using a galactose terminated lipid
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Targeting of a magnetic bionanomaterial to HepG2 human hepatocellular carcinoma cells using a galactose terminated lipid Andrew Booth1,2 Thomas P. Coxon1 Julie E. Gough2 and Simon J. Webb1 1
School of Chemistry and Manchester Institute of Biotechnology, University of Manchester, 131 Princess Street, Manchester, M1 7DN, United Kingdom 2 School of Materials, University of Manchester, M13 9PL, United Kingdom
ABSTRACT Magnetic nanoparticle-vesicle aggregates (MNPVs), a controlled release nanostructure, have been enhanced with the inclusion of a novel galactose terminated lipid for cell targeting. Quartz crystal microgravimetry with dissipation (QCM-D) demonstrated that the galactose headgroup was available to bind Erythrina Crista-galli lectin (ECL) when the lipid was incorporated into a lipid bilayer. Similarly, UV-visible spectrophotometry indicated that ECL recognized the galactose headgroup in vesicles, leading to vesicle adhesion and aggregation. Finally, confocal fluorescence microscopy was used to assess the galactose-mediated interaction of both vesicles and MNPVs with HepG2 human hepatocellular carcinoma cells expressing the asialoglycoprotein (ASGPR) galactose receptor. INTRODUCTION A wide range of processes in cultured cells, from protein expression to cell differentiation, can be directed or modulated by exposure to chemical triggers.1–3 The delivery of these chemical signals therefore forms a key tool in the development of biomaterials for applications in tissue engineering and drug delivery.4 Recent work in our group produced a magnetic nanoparticle-vesicle aggregates (MNPVs), which are capable of providing spatial and temporal control over released chemical signals in biomaterials.5 Our controlled release system, MNPVs, contain phospholipid vesicles (liposomes), which are biocompatible drug capsules that have entered clinical use (e.g. Doxil™).6 Adding synthetic lipids with modified headgroups to liposomes can improve efficacy by targeting these nanoscale structures to particular cells. MNPVs are aggregates of magnetic iron oxide nanoparticles (Fe3O4 MNPs) and vesicles that are formed by crosslinking biotin-coated nanoparticles and biotinylated vesicles with tetrameric avidin. The magnetic nanoparticles enable spatial control over chemical signal release by allowing the position of the aggregated vesicles to be manipulated using a permanent magnet. Temporal control over release is achieved by exposing the MNPVs to an alternating magnetic field (AMF) pulse, which causes the nanoparticles to generate heat via Brownian or Néel relaxation.7 This heating produces a phase transition in nearby vesicles, creating defects in the vesicle membrane that allow encapsulated drugs to diffuse out. The asialoglycoprotein receptor (ASGPR), which is specific to hepatocytes, is an attractive cell surface target that is associated with an endocytosis pathway.8 In vivo, ASGPRs remove unwanted glycoproteins from circulation; this is achieved when terminal sialic acid residues are removed to reveal galactose residues.9 For the
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