Synthesis, Characterization, and Magnetic Resonance Evaluation of Polyglycerol-Functionalized Detonation Nanodiamond Conjugated with Gadolinium(III) Complex

Abstract

A nanodiamond-polyglycerol-gadolinium(ll) conjugate has been designed and prepared as novel nanodiamond-based magnetic resonance (MR) contrast agent dispersible in physiological media. Detonation nanodiamond (dND) was first grafted with polyglycerol (PG) through ring-opening polymerization of glycidol to impart dispersibility to dND in physiological media. Since the hydroxyl group in PG serves as a scaffold for further surface functionalization, diethylenetriaminepentaacetic acid (DTPA) was immobilized on the surface of dND-PG through multistep organic transformations and Gd(III) ion was complexed in the last step. The resulting dND-PG-Gd(III) exhibited good dispersibility (> 4.5 mg/mL) and stability (> 3 months) in phosphate buffered saline (PBS). In vitro MR evaluation indicates that water proton T1 relaxivity or r1 of dND-PG-Gd(III) in aqueous solutions is larger than that of Magnevist® and the difference in the relaxivity becomes larger under weaker magnetic fields. The good dispersibility together with relatively high T1 relaxivity makes dND-PG-Gd(III) a promising contrast agent for in vivo MR imaging.

Preparation of Robust Metal‐Free Magnetic Nanoemulsions Encapsulating Low‐Molecular‐Weight Nitroxide Radicals and Hydrophobic Drugs Directed Toward MRI‐Visible Targeted Delivery

“…To evaluate the relaxation rate enhancement by the nitroxide‐based magnetic nanoemulsions, the longitudinal relaxation rate ( r 1 ) was determined from the relaxation times as a function of concentration by using the spin‐echo method at 4.7 T with respect to the unloaded and 7 ‐loaded nanoemulsions: linear regression analysis yielded r 1 =0.12 and 0.16 m m −1 s −1 , respectively (Figures b and c). These r 1 values were less than that of Magnevist [a Gd III complex agent] in deionized water (4.0 m m −1 s −1 at 4.7 T), but comparable or larger than those for ordinary water‐soluble small mononitroxide molecules (∼0.1 m m −1 s −1 at 4.7 T) . However, the good linear relationship between the T 1 contrast enhancement and the concentration of nitroxyl groups increases the significance of our nanoemulsions for biomedical application .…”

Platinum on Nanodiamond: A Promising Prodrug Conjugated with Stealth Polyglycerol, Targeting Peptide and Acid‐Responsive Antitumor Drug

“…In the 1 H-NMR spectra shown in Figure 2 B, [ 35,36 ] the aromatic and methyl hydrogens at the tosyl group are observed at 7.7 and 7.4 ppm, and 2.3 ppm in addition to the PG hydrogens at 3.6 ppm. Since only S→O functionality was characterized on the IR (Figure 1 B), the 1 H-NMR spectrum (Figure 2 B) complements the IR in the characterization of ND-PG-OTs.…”

“…[ 25,35,36 ] Carboxyl groups were introduced in ND-PG-N 3 as ligands for the Ptbased drug by nucleophilic ring-opening of succinic anhydride at the hydroxyl groups. [ 25,35,36 ] Carboxyl groups were introduced in ND-PG-N 3 as ligands for the Ptbased drug by nucleophilic ring-opening of succinic anhydride at the hydroxyl groups.…”

“…After the reaction of ND-PG-OTs with sodium azide, the peaks from the tosyl group disappeared in Figure 2 C, indicating the complete substitution of the tosyl group. 3.4 ppm is assigned to the methylene hydrogens adjacent to azido groups of the ND-PG-N 3 , [ 36,62 ] indicating the nucleophilic substitution of tosylate by azido. 3.4 ppm is assigned to the methylene hydrogens adjacent to azido groups of the ND-PG-N 3 , [ 36,62 ] indicating the nucleophilic substitution of tosylate by azido.…”

“…[ 19 ] In this context, it is proposed that polyglycerol (PG) [ 20 ] is a better alternative to PEG for biomedical applications of nanoparticle [ 21 ] in terms of biocompatibility, solubility and stability in physiological environment, and extensibility for further chemical derivatization. [ 19,29,30 ] To take advantage of the above characteristics of PG, PG-coating has been extensively applied quite recently to nanoparticles such as superparamagnetic iron oxide nanoparticle, [ 25,31,32 ] silica-encapsulated iron oxide nanoparticle, [ 33 ] nanodiamond (ND), [ 24,[34][35][36] zinc oxide nanoparticle, [ 26 ] carbon nanotubes, [37][38][39][40] quantum dots, [ 41 ] Fe@ Au nanoparticles [ 42 ] and mesoporous silica nanoparticles, [ 43 ] and even stem cell. [ 19,29,30 ] To take advantage of the above characteristics of PG, PG-coating has been extensively applied quite recently to nanoparticles such as superparamagnetic iron oxide nanoparticle, [ 25,31,32 ] silica-encapsulated iron oxide nanoparticle, [ 33 ] nanodiamond (ND), [ 24,[34][35][36] zinc oxide nanoparticle, [ 26 ] carbon nanotubes, [37][38][39][40] quantum dots, [ 41 ] Fe@ Au nanoparticles [ 42 ] and mesoporous silica nanoparticles, …”