A new magnetic resonance imaging contrast agent loaded into poly(lacide-co-glycolide) nanoparticles for long-term detection of tumors

Abstract

The incorporation of a lipophilic Gd chelate (GdDO3A-C12) in biocompatible PLGA poly(D, L-lactide-co-glycolide) nanoparticles was explored as an approach to increase the relaxivity of contrast agents for magnetic resonance imaging. By nanoprecipitation, it was possible to obtain PEGylated gadolinium nanoparticles (mean diameter of 155 nm) with high Gd loading (1.1 × 10(4) Gd centers per nanoparticle). The corresponding GdDO3AC12 ⊂ NPs nanoparticles exhibited an enhanced relaxivity (up to sixfold greater than DOTAREM® at 40 MHz) because the nanoparticle framework constrained the lipophilic Gd chelate motion and favorably impacted the Gd chelate rotational correlation time. T1-weighted imaging at 3 T on phantoms showed enhanced contrast for the GdDO3AC12 ⊂ NPs. Importantly, Gd chelate leakage was almost nonexistent, which suggested that these GdDO3AC12 ⊂ NPs could be useful for long-term MRI detection.

Silicon Wafer Functionalization with a Luminescent Tb(III) Coordination Complex: Synthesis, Characterization, and Application to the Optical Detection of NO in the Gas Phase

“…After purification, TbL was recovered in 80% yield (Scheme 1). Tb(III) complexation was demonstrated using IR spectroscopy (Figure S1), by the weakening of the carbonyl vibration from 1715 cm −1 for DOTAGA to 1594 cm −1 for TbL, as expected for a carboxylate coordination to the metal cation [26]. Moreover, the TbL complex exhibited an additional vibration at 1724 cm −1 confirming the presence of the free COOH group, uncoordinated to the metal.…”

A Novel Class of 1H‐MRI Contrast Agents Based on the Relaxation Enhancement Induced on Water Protons by 14N‐Containing Imidazole Moieties

“…On this basis, the herein‐considered imidazole‐containing polymers were conjugated to biocompatible polymers such as polylactic and glycolic acid (PLGA), in order to form stable nanoparticles containing structured water in their inner cavities. Once administered in vivo these nanosized particles are expected to act as vascular and extra‐vascular agents (in the presence of fenestrated capillaries), in analogy to what is observed for other NPs such as those based on iron oxides [32] or those based on PLGA‐containing GBCAs [33, 34] . In addition, the 14 N‐QPs of histidine‐containing peptides may act as pH sensors, in turn providing valuable information on tumour cell metabolism.…”

Encapsulation of Paramagnetic Chelates in Perfluorcarbon-loaded Fractal Nanoparticles Enables Modulation of Fluorine-19 and Proton Magnetic Resonance Imaging Signal

“…As gadolinium-agents we used two different hydrophobic gadolinium chelates that differ only in the length of a hydrophobic linker (Figure 1). 34 The chelates are hydrophobic, but not fluorophilic, and therefore should remain in the hydrophobic PLGA matrix.…”