An all-in-one nanoparticle (AION) contrast agent for breast cancer screening with DEM-CT-MRI-NIRF imaging

Abstract

Conventional X-ray mammography has low diagnostic sensitivity for women with dense breasts. As a result, alternative contrast-enhanced screening tools such as dual energy mammography (DEM), computed tomography (CT), magnetic resonance imaging (MRI), and near-infrared fluorescence (NIRF) imaging are being used or investigated for these women. However, currently available contrast agents are non-ideal, have safety issues, and each imaging technique requires a different contrast agent. We therefore sought to develop a multimodal contrast agent that is functional for each breast imaging modality to simplify the diagnosis process and address the issues of existing contrast agents. Herein, we present a novel "all-in-one" nanoparticle (AION) multimodal imaging probe that has potent DEM, CT, MRI, and NIRF contrast properties and improved biocompatibility. AION were formed by co-encapsulation of a near-infrared fluorophore (DiR), silver sulfide nanoparticles (Ag2S-NP), and iron oxide nanoparticles (IO-NP) in PEGylated micelles. AION showed negligible cytotoxicity, which was in agreement with its minimal silver ion release profiles. AION generated strong contrast with all imaging modalities as demonstrated in phantom imaging. AION allowed in vivo tumor imaging as evidenced by the increase in contrast after injection. This study indicates the potential of AION as an effective multimodal contrast agent for breast cancer diagnosis with a range of imaging methods.

A hybrid lipid membrane coating “shape-locks” silver nanoparticles to prevent surface oxidation and silver ion dissolution

“…The hybrid lipid coating anchored with PT or DT shields the AgNPs from undergoing rapid Ag + ion dissolution that is observed with elemental Ag-based nanoparticles and Ag 2 S nanoparticles coated with a lipid and lipid-PEG layer that leach more Ag + at lower pH. 70,103,119 Consequently, the relative stability at physiological and pH 5 introduces Ag-SOA-PC-HT nanoparticles as a potential platform for bioimaging or drug delivery applications lessening concerns that the AgNPs will undergo Ag + ion dissolution in lysosomal compartments once taken up into cells and induce toxicity.…”

“…Other applications where the presence of Ag + ions is unwanted include those where AgNPs are used as imaging agents for X-ray CT, 70,71 photoacoustic, 72 and optical coherence tomography (OCT) 73 or incorporated into devices such as orthopedic implants, 74 or used as drug delivery vehicles. 75,76 AgNP-based imaging agents that undergo surface oxidation and Ag + ion dissolution result in a change in the size and shape, which are physicochemical features that affect the optical and light scattering properties of AgNPs.…”

“…To protect the AgNPs from surface oxidation and instability, AgNPs have been modied with covalent organic ligands such as polyvinylpyrrolidone (PVP), 64 lipids, 70 and polyethylene glycol (PEG), [79][80][81][82] or thiolated PEG 83 as well as inorganic substrates such as gold 79 or silica core-shell. 84,85 Alloys comprised of silver, gold, and chromium have also been shown to enhance the stability of AgNPs 79,86 or other metal oxides.…”

“…87 Depending on the type of AgNPs and method of surface protection, stability studies show that the AgNPs are stable from 1 week to 100 days without a change in the size or shape in water or citrate buffer. 70,79,86 AgNPs with the organic surface coating are not very stable for long periods compared to those with an inorganic surface layer that shields the AgNP core. These design strategies are great steps towards controlling Ag + ion dissolution and preventing AgNPs from undergoing surface oxidation in a variety of media.…”

Multimodal imaging for tumour characterization from micro‐ to macroscopic level using a newly developed dorsal chamber designed for long‐term follow‐up

“…In addition, no publication describes photonic, ultrasound and MRI acquisitions all using the same dorsal chamber model. Cross‐correlating multiple parameters obtained from a unique individual should constitute a major advance for 4D mapping of tumour processes, both during disease progression and for the evaluation of novel anti‐cancer therapies, especially as new targeted and multimodal contrast agents are under development to refine the resolution and specificity of detection.…”