A comparative analysis of EGFR-targeting antibodies for gold nanoparticle CT imaging of lung cancer

Abstract

Computed tomography (CT) is the standard imaging test used for the screening and assessment of suspected lung cancer, but distinguishing malignant from benign nodules by CT is an ongoing challenge. Consequently, a large number of avoidable invasive procedures are performed on patients with benign nodules in order to exclude malignancy. Improving cancer discrimination by non-invasive imaging could reduce the need for invasive diagnostics. In this work we focus on developing a gold nanoparticle contrast agent that targets the epidermal growth factor receptor (EGFR), which is expressed on the cell surface of most lung adenocarcinomas. Three different contrast agents were compared for their tumor targeting effectiveness: non-targeted nanoparticles, nanoparticles conjugated with full-sized anti-EGFR antibodies (cetuximab), and nanoparticles conjugated with a single-domain llama-derived anti-EGFR antibody, which is smaller than the cetuximab, but has a lower binding affinity. Nanoparticle targeting effectiveness was evaluated in vitro by EGFR-binding assays and in cell culture with A431 cells, which highly express EGFR. In vivo CT imaging performance was evaluated in both C57BL/6 mice and in nude mice with A431 subcutaneous tumors. The cetuximab nanoparticles had a significantly shorter blood residence time than either the non-targeted or the single-domain antibody nanoparticles. All of the nanoparticle contrast agents demonstrated tumor accumulation; however, the cetuximab-targeted group had significantly higher tumor gold accumulation than the other two groups, which were statistically indistinguishable from one another. In this study we found that the relative binding affinity of the targeting ligands had more of an effect on tumor accumulation than the circulation half life of the nanoparticles. This study provides useful insight into targeted nanoparticle design and demonstrates that nanoparticle contrast agents can be used to detect tumor receptor overexpression. Combining receptor status data with traditional imaging characteristics has the potential for better differentiation of malignant lung tumors from benign lesions.

Magnetic Functionalized Nanoparticles for Biomedical, Drug Delivery and Imaging Applications

“…AuNPs also have use in cell imaging for examining movement of nanoparticles within cells when conjugated with various cargoes. Figure 6 is a darkfield imaging of A431 lung cancer cells treated with AuNPs that target epidermal growth factor receptor, and the bright areas within the cells are the nanoparticles indicating their locations within the cells [144].

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Introduction to Editorial Board Member: Professor Jennifer L. West

“…For their invention, West and Halas were named co‐recipients of the Best Discovery of 2003 Award from Nanotechnology Now and they also were named 2005 Outstanding Women of Achievement in Science and Technology by the YWCA of Houston 4,5 . Since the original breakthrough of photothermal therapy, West has further contributed to advancements in nanomedicine by developing numerous innovative nanotechnologies for multi‐modal imaging enhancement, light‐responsive drug delivery, and more 6–16 …”

Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

“…After in vivo injection, the VHH‐AuNPs control non‐targeted PEG‐AuNPs showed equivalent tumor accumulation, while the C225‐AuNPs exhibited much higher accumulation. Further, the C225‐AuNPs showed significantly increased tumor uptake due to specific tumor targeting (Ashton et al, 2018).…”