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

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 n...

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Bibliographic Details
Published in:Oncotarget 2016-06, Vol.7 (24), p.36002-36013
Main Authors: Otis, James B, Zong, Hong, Kotylar, Alina, Yin, Anna, Bhattacharjee, Somnath, Wang, Han, Baker, Jr, James R, Wang, Su He
Format: Article
Language:English
Subjects:
A549 Cells
Cell Line, Tumor
Cell Tracking - methods
Dendrimers - chemistry
Heterocyclic Compounds, 1-Ring - chemistry
Humans
Metal Nanoparticles - chemistry
Microscopy, Confocal
Neoplasms - diagnosis
Neoplasms - genetics
Neoplasms - metabolism
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - immunology
Receptor, ErbB-2 - metabolism
Research Paper
Trastuzumab - chemistry
Trastuzumab - immunology
Trastuzumab - metabolism
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.9081