Applications of Nanoparticle-Antibody Conjugates in Immunoassays and Tumor Imaging

Abstract

Modern diagnostic technologies rely on both in vitro and in vivo modalities to provide a complete understanding of the clinical state of a patient. Nanoparticle-antibody conjugates have emerged as promising systems to confer increased sensitivity and accuracy for in vitro diagnostics (e.g., immunoassays). Meanwhile, in vivo applications have benefited from the targeting ability of nanoparticle-antibody conjugates, as well as payload flexibility and tailored biodistribution. This review provides an encompassing overview of nanoparticle-antibody conjugates, from chemistry to applications in medical immunoassays and tumor imaging, highlighting the underlying principles and unique features of relevant preclinical applications employing commonly used imaging modalities (e.g., optical/photoacoustics, positron-emission tomography, magnetic resonance imaging, X-ray computed tomography).

Keywords: antibody conjugates; immunoassay; nanoparticle; tumor imaging.

Fig. 1

Structure of IgG molecule and its fragments: F(ab’)₂ fragment, Fab fragment, and single-chain variable fragment (scFv)

Fig. 2.

Schematic representation of a sandwich immunoassay leveraging nanoparticle-antibody conjugates for surface plasmon resonance (SPR)

Fig. 3

Schematic representation of an immunoassay leveraging nanoparticle-antibody conjugates for localized surface plasmon resonance (LSPR) (48)

Fig. 4

Whole-body fluorescence intensity distribution in a representative leukemic mouse 24-h post-injection of cy5.5-anti-cD20 NPs and cy5.5-untargeted NPs. The circles enclose the tumors (49)

Fig. 5

In vivo MR tumor imaging post i.v. administration of scFv-IONPs or PEG-IONPs in N87 or SUIT2 tumor-bearing mice. a In vivo MR images (axial) of scFv-IONP, PEG-IONP, or scFv-IONP mixed with trastuzumab in N87 (HER2+) and SUIT2 (HER2−) bearing mice. b Signal intensity of tumors shown as the ratio of object-to-phantom. *p < 0.05 (66)

Fig. 6

X-ray computed tomography images of KPL-4 murine xenografts demonstrating tumor contrast post 15 nm anti-HER2 gold nanoparticles intravenous administration (108)

Fig. 7

In vivo PET imaging in xenograft breast cancer models following administration of HER2-targeted radiolabeled C’ dots (i.v.). Serial coronal and axial tomographic PET images acquired at 2, 24, 48, and 72 h post i.v. injection. a Targeted group: ⁸⁹Zr-DFO-scFv-PEG-Cy5-C’ dots in BT-474 tumor model, b non-targeted group: ⁸⁹Zr-DFO-Ctr/scFv-PEG-Cy5-C’ dots in BT-474 tumor model, and c targeted group: ⁸⁹Zr-DFO- scFv-PEG-Cy5-C’ dots in MDA-MB-231 tumor model. H heart, B bladder, L liver (121)