title: Engineering hepatitis B virus core particles for targeting HER2 receptors in vitro and in vivo.
abstract: Hepatitis B Virus core (HBc) particles have been studied for their potential as drug delivery vehicles for cancer therapy. HBc particles are hollow nano-particles of 30-34 nm diameter and 7 nm thick envelopes, consisting of 180-240 units of 21 kDa core monomers. They have the capacity to assemble/dis-assemble in a controlled manner allowing encapsulation of various drugs and other biomolecules. Moreover, other functional motifs, i.e. receptors, receptor binding sequences, peptides and proteins can be expressed. This study focuses on the development of genetically modified HBc particles to specifically recognise and target human epidermal growth factor receptor-2 (HER2)-expressing cancer cells, in vitro and in vivo, for future cancer therapy. The non-specific binding capacity of wild type HBc particles was reduced by genetic deletion of the sequence encoding arginine-rich domains. A specific HER2-targeting was achieved by expressing the ZHER2affibodies on the HBc particles surface. In vitro studies showed specific uptake of ZHER2-ΔHBc particles in HER2 expressing cancer cells. In vivo studies confirmed positive uptake of ZHER2-ΔHBc particles in HER2-expressing tumours, compared to non-targeted ΔHBc particles in intraperitoneal tumour-bearing mice models. The present results highlight the potential of these nanocarriers in targeting HER2-positive metastatic abdominal cancer following intra-peritoneal administration.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: izzat_fahimuddin.bin_mohamed_suffian@kcl.ac.uk.
authors.forename: Izzat Fahimuddin Bin
authors.initials: IFB
authors.lastname: Mohamed Suffian
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: julie.tzu-wen.wang@kcl.ac.uk.
authors.forename: Julie Tzu-Wen
authors.initials: JT
authors.lastname: Wang
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: naomi.hodgins@kcl.ac.uk.
authors.forename: Naomi O
authors.initials: NO
authors.lastname: Hodgins
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: rebecca.klippstein_martin@kcl.ac.uk.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Klippstein
authors.affiliation: Randall Division of Cell & Molecular Biophysics, King's College London, New Hunt's House, London SE1 1UL, UK. Electronic address: mitla.garcia@kcl.ac.uk.
authors.forename: Mitla
authors.initials: M
authors.lastname: Garcia-Maya
authors.affiliation: Randall Division of Cell & Molecular Biophysics, King's College London, New Hunt's House, London SE1 1UL, UK. Electronic address: paul.brown@kcl.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Brown
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan. Electronic address: nyuya@landscape.kobe-u.ac.jp.
authors.forename: Yuya
authors.initials: Y
authors.lastname: Nishimura
authors.affiliation: Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Electronic address: hamed.heidari@uantwerpen.be.
authors.forename: Hamed
authors.initials: H
authors.lastname: Heidari
authors.affiliation: Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium. Electronic address: sara.bals@uantwerpen.be.
authors.forename: Sara
authors.initials: S
authors.lastname: Bals
authors.affiliation: Centre for Molecular Oncology, Bart's Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK. Electronic address: j.k.sosabowski@qmul.ac.uk.
authors.forename: Jane K
authors.initials: JK
authors.lastname: Sosabowski
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan. Electronic address: ochiaki@port.kobe-u.ac.jp.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Ogino
authors.affiliation: Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan. Electronic address: akondo@kobe-u.ac.jp.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kondo
authors.affiliation: Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London SE1 9NH, UK. Electronic address: khuloud.al-jamal@kcl.ac.uk.
authors.forename: Khuloud T
authors.initials: KT
authors.lastname: Al-Jamal
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000737:chemistry / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism*; D014771:Virion / Q000235:genetics* / Q000378:metabolism*
chemical_list: D053769:Nanocapsules; D018719:Erb-b2 Receptor Tyrosine Kinases; D011994:Recombinant Proteins; D014758:Viral Core Proteins; C508053:ERBB2 protein, human
keywords: Active targeting; Affibody; Hepatitis B virus core particles; Human epidermal growth factor receptor 2; Virus-like particles