Biofunctionalized Gadolinium-Containing Prussian Blue Nanoparticles as Multimodal Molecular Imaging Agents

Abstract

Molecular imaging agents enable the visualization of phenomena with cellular and subcellular level resolutions and therefore have enormous potential in improving disease diagnosis and therapy assessment. In this article, we describe the synthesis, characterization, and demonstration of core-shell, biofunctionalized, gadolinium-containing Prussian blue nanoparticles as multimodal molecular imaging agents. Our multimodal nanoparticles combine the advantages of MRI and fluorescence. The core of our nanoparticles consists of a Prussian blue lattice with gadolinium ions located within the lattice interstices that confer high relaxivity to the nanoparticles providing MRI contrast. The relaxivities of our nanoparticles are nearly nine times those observed for the clinically used Magnevist. The nanoparticle MRI core is biofunctionalized with a layer of fluorescently labeled avidin that enables fluorescence imaging. Biotinylated antibodies are attached to the surface avidin and confer molecular specificity to the nanoparticles by targeting cell-specific biomarkers. We demonstrate our nanoparticles as multimodal molecular imaging agents in an in vitro model consisting of a mixture of eosinophilic cells and squamous epithelial cells. Our nanoparticles specifically detect eosinophilic cells and not squamous epithelial cells, via both fluorescence imaging and MRI in vitro. These results suggest the potential of our biofunctionalized Prussian blue nanoparticles as multimodal molecular imaging agents in vivo.

Composite iron oxide–Prussian blue nanoparticles for magnetically guided T₁-weighted magnetic resonance imaging and photothermal therapy of tumors

“…Finally, studies conducted to calculate the photothermal conversion efficiency ( Figure 4D) demonstrated that the nanoparticles had a photothermal conversion efficiency of 16.1%, which is consistent with the previously determined photothermal conversion efficiency of Prussian blue nanoparticles (around 20%) 35 despite others). 32,38,39 Similarly, T2W scans demonstrated that the Fe 3 O 4 @GdPB nanoparticles generated increased contrast in a concentration-dependent manner ( Figure 3B), ie, increased darkening with increasing concentrations, similar to Fe 3 O 4 nanoparticles, which have been well-described in the literature. 5,6 Based on image processing of multiple T1W and T2W scans, we generated relaxation time plots as a function of the contrast agent, namely Gd 3+ ions for GdPB ( Figure 3C) and Fe 3 O 4 @GdPB ( Figure 3D), and Fe for Fe 3 O 4 ( Figure 3E) and Fe 3 O 4 @GdPB ( Figure 3F).…”

“…The size (hydrodynamic diameter) and charge (zeta potential) distributions of the Fe 3 O 4 @GdPB nanoparticles were compared with both Fe 3 O 4 and GdPB nanoparticles (previously synthesized by us) 32,33 using dynamic light scattering on a Zetasizer Nano ZS (Malvern Instruments, Malvern, UK). Multiday stability of the Fe 3 O 4 @GdPB nanoparticles in ultrapure water was assessed by measuring their hydrodynamic size distributions every 24 hours over 5 days using dynamic light scattering.…”

Prussian blue/serum albumin/indocyanine green as a multifunctional nanotheranostic agent for bimodal imaging guided laser mediated combinatorial phototherapy

“…The clinically used T 1 contrast agent, Magnevist (gadolinium diethylenetriamine pentaacetic acid, Bayer HealthCare Pharmaceuticals Inc.), has an r 1 value of 4.3 mM − 1 s − 1 , which is higher than our PB-BSA nanoparticle [35]. But, recent studies suggested the longitudinal relaxivity of PB nanoparticles can be easily enhanced by doping with paramagnetic ions such as gadolinium (Gd 3+ ) or manganese (Mn 2+ ) [40][41][42].…”

Mn2+-Doped Prussian Blue Nanocubes for Bimodal Imaging and Photothermal Therapy with Enhanced Performance

“…Therefore, many groups including ours have explored the applications of PB-based nanoagents as PTT agent for cancer treatment in animal models [20][21][22][23][24][25][26][27][28] . Further, it has been found that doping of other paramagnetic ions, such as Gd 3+ and Mn 2+ into PB could enhance its T1 contrasting ability in magnetic resonance (MR) imaging [29][30][31][32][33][34] For in vitro cell toxicity assay, 4T1 cells were seeded in 96-well plates at a density of 10 4 Bio-RAD) to determine their relative cell viability. which was diluted into 10 ml by water, was measured by ICP-AES.…”