title: Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells.
abstract: Although many breast and lung cancers overexpress human epidermal growth factor receptor-2 (HER-2), no methods currently exist for effective and early detection of HER-2-positive cancers. To address this issue, we designed and synthesized dendrimer-based novel nano-imaging agents that contain gold nanoparticles (AuNPs) and gadolinium (Gd), conjugated with the humanized anti-HER-2 antibody (Herceptin). Generation 5 (G5) polyamidoamine (PAMAM) dendrimers were selected as the backbone for the nano-imaging agents due to their unique size, high ratio of surface functional groups and bio-functionality. We modified G5 PAMAM dendrimer surface with PEG and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators to encapsulate AuNPs and complex Gd. These dendrimer entrapped AuNPs were further conjugated with Herceptin through copper-catalyzed azide- alkyne click reaction to construct the nano-imaging agent Au-G5-Gd-Herceptin. The targeted nano-imaging agent bound selectively to HER-2 overexpressing cell lines, with subsequent internalization into the cells. More importantly, non-targeted nano-imaging agent neither bound nor internalized into cells overexpressing HER-2. These results suggest that our approach could provide a platform to develop nano-diagnostic agents or nano-therapeutic agents for early detection and treatment of HER-2-positive cancers.
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Otis
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Zong
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Alina
authors.initials: A
authors.lastname: Kotylar
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Yin
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Somnath
authors.initials: S
authors.lastname: Bhattacharjee
authors.affiliation: Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, P.R.China.
authors.forename: Han
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
authors.affiliation: Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Su He
authors.initials: SH
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D045744:Cell Line, Tumor; D058948:Cell Tracking / Q000379:methods*; D050091:Dendrimers / Q000737:chemistry*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000068878:Trastuzumab / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D050091:Dendrimers; D006573:Heterocyclic Compounds, 1-Ring; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C104700:PAMAM Starburst; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
keywords: PAMAM dendrimer; anti-HER2-monoclonal antibody; gold nanoparticles; imaging agent; targeting