Assembly of near infra-red emitting upconverting nanoparticles and multiple Gd(iii)-chelates as a potential bimodal contrast agent for MRI and optical imaging

Abstract

Linking multiple paramagnetic gadolinium(III)-chelates based on the 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetate (DOTA) ligand to the surface of NaGdF4:Yb(3+),Tm(3+) upconverting nanoparticles with an average particle size of 20 nm resulted in an assembly that has favorable properties for bimodal Magnetic Resonance Imaging (MRI) and Optical Imaging (OI). An improved synthetic pathway was used to couple the paramagnetic precursor to the nanoparticles. The nanoparticles were rendered water dispersible via citrate capping, leaving one acid group free for amide coupling with the mono-amino precursor of the DOTA ligand. Luminescence spectroscopy measurements have shown that the excitation of the nanoconstruct at 980 nm resulted in intense upconverted emission of thulium(III) at 800 nm. The assembly of several paramagnetic centers on the nanoparticle scaffold reduces the overall tumbling rate, resulting in enhanced longitudinal relaxation times and improved relaxivity. The proton NMRD profiles show a characteristic hump at higher frequencies, which is caused by the slow rotation of the nanoconstruct, resulting in r1 values of 25 mM(-1) s(-1) per gadolinium(III)-ion at 60 MHz and 310 K. This is a significant improvement compared to the Gd-DO3A-ethylamine precursor (4) for which a value of r1 of 3.23 mM(-1) s(-1) was observed under the same conditions. Theoretical fitting by two different approaches showed an increase of τR from 57.3 ps for the Gd-DO3A-ethylamine precursor (4) to 392.0 ps for the nanoconstruct, which is responsible for the overall substantial increase in relaxivity.

Multifunctional β-NaGdF4:Ln3+ (Ln = Yb, Er, Dy) nanoparticles with NIR to visible upconversion and high transverse relaxivity: a potential bimodal contrast agent for high-field MRI and optical imaging

“…1) were synthesized by the thermal decomposition of Ln 3+ -triuoroacetate precursors at the temperature of 310-320 C under an argon stream. 22,[26][27][28] A detailed experimental procedure is presented in the ESI. † For their application in the eld of biology, UCNPs should be hydrophilic and biocompatible.…”

“…To contribute to this target, the oleate groups were replaced by citrate groups which are hydrophilic and allow further functionalization because of the targetable COO À group. 22 FT-IR spectra were recorded for all the AC/AS-UCNPs before and aer the exchange of oleate and citrate groups to see whether all the oleate groups were replaced by citrate groups. Fig.…”

“…In the past, several attempts have been made to develop multimodal imaging agents based on UC nanoparticles. 4 The multimodal imaging agents are fabricated by the incorporation of Gd 3+ , widely used as the T 1 contrast agent in magnetic resonance imaging (MRI), 7,[20][21][22] in the crystal host lattice to develop particles that can simultaneously serve as optical and magnetic contrast agents. Zhang et al synthesized multifunctional magnetic/ upconversion luminescent mesoparticles, consisting of a Fe 3 O 4 nanoparticle core and a LaF 3 :Yb 3+ , Er 3+ nanocrystal shell, using a co-precipitation method.…”

Cancer‐Targeted Nanotheranostics: Recent Advances and Perspectives

“…Another multimodal imaging strategy is to dope specific elements in the nanoparticles or fabricate core‐shell type nanostructures. Capobianco et al incorporated Gd into UCNPs to generate excellent T 1 ‐weight MRI and fluorescence imaging . In addition, the integration of two or more agents into a single nanoplatform can also yield multimodal imaging.…”

Photoluminescent nanoplatforms in biomedical applications

“…NaYF 4 :Gd ). This was shown by Capobianco and coll [133]. The authors recently developed an Ln-UCNP-Gd-chelate bimodal probe by covalent conjugation of Gd-DOTA molecules to citrate-capped NaGdF 4 Ln-UCNPs.…”