Development of anti-HER2 fragment antibody conjugated to iron oxide nanoparticles for in vivo HER2-targeted photoacoustic tumor imaging

• Published in: Nanomedicine Vol. 11; no. 8; pp. 2051 - 2060
• Main Authors: Kanazaki, Kengo, MS, Sano, Kohei, PhD, Makino, Akira, PhD, Shimizu, Yoichi, PhD, Yamauchi, Fumio, PhD, Ogawa, Satoshi, MS, Ding, Ning, BS, Yano, Tetsuya, BS, Temma, Takashi, PhD, Ono, Masahiro, PhD, Saji, Hideo, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2015
• Subjects: Animals; Cell Line, Tumor; Contrast Media - chemistry; Contrast Media - pharmacokinetics; Female; Ferric Compounds - chemistry; Ferric Compounds - pharmacokinetics; HER2; Humans; Immunoconjugates - chemistry; Immunoconjugates - pharmacokinetics; Internal Medicine; Iron oxide nanoparticle; Mice, Inbred BALB C; Mice, Nude; Nanoparticles - analysis; Nanoparticles - chemistry; Neoplasms - diagnosis; Photoacoustic imaging; Photoacoustic Techniques - methods; Receptor, ErbB-2 - analysis; Single-Chain Antibodies - chemistry; Single-Chain Antibodies - pharmacokinetics; Single-chain Fv; Tissue Distribution; Iron oxide nanoparticle; Photoacoustic imaging; HER2; Single-chain Fv
• ISSN: 1549-9634; 1549-9642
• DOI: 10.1016/j.nano.2015.07.007

Abstract Photoacoustic (PA) imaging is a promising imaging modality that provides biomedical information with high sensitivity and resolution. Iron oxide nanoparticles (IONPs) have been regarded as remarkable PA contrast agents because of their low toxicity and biodegradable properties. However, IONP delivery is restricted by its modest leakage and retention in tumors. In this study, we designed IONPs (20 nm, 50 nm, and 100 nm) conjugated with anti-HER2 moieties [whole IgG, single-chain fragment variable (scFv), and peptide] for HER2-targeted PA tumor imaging. The binding affinity, cellular uptake, and in vivo biodistribution were examined. We propose 20-nm anti-HER2 scFv-conjugated IONPs (SNP20) as a novel PA contrast agent. SNP20 demonstrated high affinity and specific binding to HER2-expressing cells; it selectively visualized HER2-positive tumors in PA imaging studies. These data indicate that SNP20 is a potential PA contrast agent for imaging of HER2-expressing tumors. From the Clinical Editor Iron oxide nanoparticles have been demonstrated to be good contrast agents for tumor imaging. They may also be useful in photoacoustic (PA) imaging, which can provide high sensitivity data and image resolution. The authors here coupled iron oxide nanoparticles with anti-HER2 antibody fragment and showed significant retention of these nanoparticles in tumors. This combination may provide another option for enhanced imaging of tumors.