Oncotarget

Research Papers:

Dendrimer antibody conjugate to target and image HER-2 overexpressing cancer cells

James B. Otis, Hong Zong, Alina Kotylar, Anna Yin, Somnath Bhattacharjee, Han Wang, James R. Baker Jr and Su He Wang _

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Oncotarget. 2016; 7:36002-36013. https://doi.org/10.18632/oncotarget.9081

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Abstract

James B. Otis1, Hong Zong1, Alina Kotylar1, Anna Yin1, Somnath Bhattacharjee1, Han Wang2, James R. Baker Jr1, Su He Wang1

1Department of Internal Medicine, Division of Allergy, Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan, USA

2Department of Radiology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shangai, P.R.China

Correspondence to:

Su He Wang, email: [email protected]

Keywords: anti-HER2-monoclonal antibody, gold nanoparticles, PAMAM dendrimer, imaging agent, targeting

Received: November 25, 2015     Accepted: March 31, 2016     Published: April 28, 2016

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.


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