title: Biofabricated nanoparticle coating for liver-cell targeting.
abstract: Biology routinely uses noncovalent interactions to perform complex functions that range from the molecular recognition of ligand-receptor binding to the reversible self-assembly/disassembly of hierarchical nanostructures (e.g., virus particles). Potentially, biological materials that offer such recognition and reversible self-assembly functionality can be applied to nanomedicine. Here, polysaccharides with the multifunctional polysaccharide-binding protein Concanavalin A (Con A) are coupled to create a functional nanoparticle coating. This coating is self-assembled in a layer-by-layer format by sequentially contacting a nanoparticle with Con A and the polysaccharide glycogen. In the final assembly step, a galactomannan targeting ligand is self-assembled into the coating. Evidence indicates that the mannose residues of the galactomannan backbone are responsible for assembly into the coating by Con A binding, while the galactose side chain residues are responsible for targeting to the liver-specific asialoglycoprotein receptor (ASGP-R). Binding to ASGP-R induces endocytic uptake, while the low endosomal pH triggers disassembly of the coating and release of the nanoparticle-entrapped drug. In vitro cell studies indicate that the coating confers liver-cell-specific function for both nanoparticle uptake and drug delivery. These studies extend the use of Con A to sugar-mediated and organ-specific targeting, and further illustrate the potential of biologically based fabrication for generating functional materials.
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Qu
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Jinyang
authors.initials: J
authors.lastname: Li
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Hong
authors.affiliation: Institute of Nano and Bio-polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Nano and Bio-polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai, 201804, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ren
authors.affiliation: Institute for Biosystems and Biotechnology Research and Fischell Department of Engineering, 5115 Plant Sciences Building, College Park, MD, 20742, USA.
authors.forename: Gregory F
authors.initials: GF
authors.lastname: Payne
authors.affiliation: The State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, 200237, China.|Key Laboratory for Ultrafine Materials of Ministry of Education, East China University of Science and Technology, Shanghai, 200237, China.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Liu
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000633:toxicity; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003208:Concanavalin A / Q000737:chemistry / Q000378:metabolism; D004317:Doxorubicin / Q000737:chemistry / Q000633:toxicity; D006367:HeLa Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry*; D058525:Quartz Crystal Microbalance Techniques
chemical_list: D000903:Antibiotics, Antineoplastic; D037263:Asialoglycoprotein Receptor; D003208:Concanavalin A; D004317:Doxorubicin
keywords: concanavalin A; controlled drug delivery; liver targeting; self-assembly; sugar-lectin interaction