Label-Free Iron Oxide Nanoparticles as Multimodal Contrast Agents in Cells Using Multi-Photon and Magnetic Resonance Imaging

Abstract

Introduction The inherent fluorescence properties of iron oxide nanoparticles (IONPs) were characterized, and their applicability for multiphoton imaging in cells was tested in combination with their magnetic resonance imaging (MRI) capabilities. Methods Superparamagnetic iron oxide nanoparticles were synthesized and subsequently coated with polyethylene glycol to make them water-dispersible. Further characterization of the particles was performed using Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), dynamic light scattering (DLS), superconducting quantum interference device (SQUID) and magnetic resonance relaxivity measurements. MRI and fluorescence properties of bare IONPs were first studied in solution and subsequently in A549-labeled cells. Results The particles, with a core size of 11.3 ± 4.5 nm, showed a good negative MRI contrast in tissue-mimicking phantoms. In vitro studies in mammalian A549 cells demonstrate that these IONPs are biocompatible and can also produce significant T2/T2* contrast enhancement in IONPs-labeled cells. Furthermore, excitation-wavelength dependent photoluminescence was observed under one- and two-photon excitation. Discussion The obtained results indicated that IONPs could be used for fluorescence label-free bioimaging at multiple wavelengths, which was proven by multiphoton imaging of IONPs internalization in A549 cancer cells.

Recent trends in preparation and biomedical applications of iron oxide nanoparticles

“…twofold of SPIONs@PEI-CPs were taken into A549 cells with the applied external MF, and remarkable inhibited the growth of A549 cells [ 72 ]. IONPs with core size of 11.3 ± 4.5 nm (below 250 μg Fe/mL) were internalized by A549 cells without causing any significant morphology changes, which suggested this IONPs was suitable for MRI contrast agents in vitro [ 73 ].…”

Using a Förster-resonance energy transfer (FRET)-based detection system (FedEcs) to monitor nanoparticle cargo delivery to the brain

“…Magnetic nanoparticles, Nanomag®-D (Micromod, Rostok, Germany), diameter 180 nm, PEG 2000 coated, were injected slowly at a volume of 6 µl/g body weight via a femoral artery catheter. Since iron oxide is a magnetite and each particle acts as an individual magnetic domain 37 , we expected to block the vessels via interaction between a magnet and blood-circulated MNPs. Safety, biocompatibility, and physical parameters of these MNPs were described previously 10 .…”

“…In order to preserve the same imaging orientation for EM from the 2-photon experiment, the block was trimmed parallel to the cortical surface. The advantage of MNPs is to be seen label-free in light, fluorescent and electron microscopies 37 . Thereby, the correlation strategy relied on electron-dense magnetic particles and further anatomical landmarks like vascular patterns (Figure S05, B) and regions of MNP leftovers in the reperfused area, far outside of the ROI.…”

Advances in optical molecular imaging for neural visualization

“…In addition, optical molecular imaging technology can potentially visualize the parts that the fluorescent agent can reach during the operation. Recently, researchers have proposed a multimodal tumor diagnosis strategy by combining MRI and fluorescence imaging systems ( McCann et al, 2009 ; Reynders et al, 2021 ; Song et al, 2021 ). This approach has demonstrated unique advantages in the multiple imaging of target tissues in vivo .…”