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Novel nanogels, characterized by high stability and incorporating macrocyclic chelates of Gd(III) and Dy(III), were synthesized and assessed for their effectiveness as T1 and T2 relaxation agents, respectively. In this specific design, we employed octacoordinated bifunctional Gd‐1,7‐DOTAGA2 chelate to cross‐link chitosan chains. The results revealed that the sample exhibited a relaxivity value at clinical magnetic field strengths (1.5 T), approximately seven times higher than that of currently available clinical contrast agents and good MRI contrast efficacy at both 7.1 and 1 T. Furthermore, the nanogel displayed excellent stability in biological fluids, with no discernible interactions with serum biomolecules and no release of metal. In addition to Gd(III)‐based probes commonly used as T1 positive contrast agents, the nanogel with the corresponding Dy‐1,7‐DOTAGA2 chelate was prepared to explore its potential as a T2 MRI probe. Dy‐based nanogel demonstrated notably elevated transverse relaxivity values compared to the free chelate at high magnetic fields (>3 T) and significant T2 MRI contrast at 7.1 T, a capability often lacking when employing an equivalent concentration of a low‐molecular‐weight Dy(III) complex. The characterization of paramagnetic complexes was completed through the measurement of 1H NMRD profiles and 17O NMR data. [ABSTRACT FROM AUTHOR]

Magnetic Resonance Imaging (MRI) T1 contrast agents based on Fe(III) as an alternative to Gd‐based compounds have been under intense scrutiny in the last 6–8 years and a number of nanostructures have been designed and proposed for in vivo diagnostic and theranostic applications. Excluding the large family of superparamagnetic iron oxides widely used as T2‐MR imaging agents that will not be covered by this review, a considerable number and type of nanoparticles (NPs) have been employed, ranging from amphiphilic polymer‐based NPs, NPs containing polyphenolic binding units such as melanin‐like or polycatechols, mixed metals such as Fe/Gd or Fe/Au NPs and perfluorocarbon nanoemulsions. Iron(III) exhibits several favorable magnetic properties, high biocompatibility and improved toxicity profile that place it as the paramagnetic ion of choice for the next generation of nanosized MRI and theranostic contrast agents. An analysis of the examples reported in the last decade will show the opportunities for relaxivity and MR‐contrast enhancement optimization that could bring Fe(III)‐doped NPs to really compete with Gd(III)‐based nanosystems. This article is categorized under:Diagnostic Tools > In Vivo Nanodiagnostics and ImagingDiagnostic Tools > Diagnostic NanodevicesTherapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease [ABSTRACT FROM AUTHOR]

New peptide-based hydrogels incorporating Gd(III) chelates with different hydration states, molecular structures and overall negative charges ([Gd(BOPTA)]2−), [Gd(DTPA)]2−, and ([Gd(AAZTA)]−) were prepared and characterized. N-terminal Fmoc- or acetyl-derivatized hexapeptides (K1, K2 and K3) containing five aliphatic amino acids (differently ordered Gly, Ala, Val, Leu and Ile) and a charged lysine at the amidated C-terminal were used for the formation of the hydrogels. Particular attention was paid to the investigation of the morphological and rheological properties of the nanoparticles, in addition to the assessment of the ability (relaxivity) of the confined complexes to accelerate the longitudinal relaxation rate of the water protons localized in the polymeric network. The relaxivity values at high magnetic fields (>0.5 T) of the paramagnetic hydrogels appear to be more than five times higher than those of isolated chelates in an aqueous solution, reaching a value of 25 mmol−1 s−1 for Fmoc-K2+[Gd(BOPTA)]2− at 0.5 T and 310 K. Furthermore, an interesting trend of decrease of relaxivity with increasing the degree of rigidity of the hydrogel was observed. The type of interactions between the various complexes and the polymeric network also plays a key role in influencing the relaxivity values of the final materials. Nanogels were also obtained from the submicronization of the hydrogel containing [Gd(BOPTA)]2− chelate. Circular dichroism, dynamic light scattering and relaxometric investigations on these nanoparticles revealed the formation of nanogels endowed with higher relaxivities (r1 = 41 mM−1 s−1 at 0.5 T MHz and 310 K) than the corresponding hydrogels. [ABSTRACT FROM AUTHOR]

The first binuclear Gd‐complex of the 12‐membered pyridine‐based polyaminocarboxylate macrocyclic ligand PCTA was synthesized by C−C connection of the pyridine units through two different synthetic procedures. A dimeric AAZTA‐ligand was also synthesized with the aim to compare the relaxometric results or the two ditopic Gd‐complexes. Thus, the 1H relaxometric study on [Gd2PCTA2(H2O)4] and on [Gd2AAZTA2(H2O)4]2− highlighted the remarkable rigidity and compactness of the two binuclear complexes, which results in molar relaxivities (per Gd), at 1.5 T and 298 K of ca. 12–12.6 mM−1 s−1 with an increase of ca. 80 % at 1.5 T and 298 K (+70 % at 310 K) with respect to the corresponding mononuclear complexes. [ABSTRACT FROM AUTHOR]

The anchoring of lanthanide(III) chelates on the surface of mesoporous silica nanoparticles (MSNs) allowed their investigation as magnetic resonance imaging (MRI) and chemical exchange saturation transfer (CEST) contrast agents. Since their efficiency is strongly related to the interaction occurring between Ln-chelates and "bulk" water, an estimation of the water diffusion inside MSNs channels is very relevant. Herein, a method based on the exploitation of the CEST properties of TbDO3A-MSNs was applied to evaluate the effect of water diffusion inside MSN channels. Two MSNs, namely MCM-41 and SBA-15, with different pores size distributions were functionalized with TbDO3A-like chelates and polyethylene glycol (PEG) molecules and characterized by HR-TEM microscopy, IR spectroscopy, N2 physisorption, and thermogravimetric analysis (TGA). The different distribution of Tb-complexes in the two systems, mainly on the external surface in case of MCM-41 or inside the internal pores for SBA-15, resulted in variable CEST efficiency. Since water molecules diffuse slowly inside silica channels, the CEST effect of the LnDO3A-SBA-15 system was found to be one order of magnitude lower than in the case of TbDO3A-MCM-41. The latter system reaches an excellent sensitivity of ca. 55 ± 5 µM, which is useful for future theranostic or imaging applications. [ABSTRACT FROM AUTHOR]

Two amphiphilic mono- and dimeric GdAAZTA-like chelates composed of stable bis-aquo GdIII complexes ( q=2) linked to one (for the monomer) or two dodecyl aliphatic chains (for the dimer) were synthesized. Both chelates showed high relaxivity when incorporated into the lipid bilayer of liposomes or after interaction with human serum albumin (HSA). The ditopic complex shows a significantly decreased internal motion relative to the monomeric complex, associated with an enhanced relaxivity ( r1≈60 m m−1 s−1, at 30 MHz and 310 K). The presence of two metal-bound water molecules in fast exchange and the restricted rotational freedom make the relaxivity of this system the highest measured for paramagnetic liposomes. [ABSTRACT FROM AUTHOR]

N-Substituted aminoethyl groups were attached to 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) with the aim to design pH-responsive LnIII complexes based on the pH-dependent on/off ligation of the amine nitrogen to the metal ion. The following ligands were synthesized: AE- DO3A (aminoethyl-DO3A), MAE- DO3A ( N-methylaminoethyl-DO3A), DMAE- DO3A ( N, N-dimethylaminoethyl-DO3A) and MEM- AE- DO3A ( N-methoxyethyl- N-methylaminoethyl-DO3A). The physicochemical properties of the LnIII complexes were investigated for the evaluation of their potential applicability as magnetic resonance imaging (MRI) contrast agents. In particular, a 1H and 17O NMR relaxometric study was carried out for these GdIII complexes at two different pH values: at basic pH (pendant amino group coordinated to the metal centre) and at acidic pH (protonated amine, not interacting with the metal ion). EuIII complexes allow one to estimate the number of inner-sphere water molecules through luminescence lifetime measurements and obtain some structural information through variable-temperature (VT) high-resolution 1H NMR studies. Equilibria between differently hydrated species were found for most of the complexes at both acidic and basic pH. The thermodynamic stability of CaII, ZnII, CuII and LnIII complexes and kinetics of formation and dissociation reactions of LnIII complexes of AE- DO3A and DMAE- DO3A were investigated showing stabilities comparable to currently approved GdIII-based CAs. In detail, higher total basicity (Σlog KiH) and higher stability constants of LnIII complexes were found for AE- DO3A with respect to DMAE- DO3A (i.e., log KGd- AE-DO3A=22.40 and log KGd- DMAE-DO3A=20.56). The transmetallation reactions of GdIII complexes are very slow (Gd- AE- DO3A: t1/2=2.7×104 h; Gd- DMAE- DO3A: 1.1×105 h at pH 7.4 and 298 K) and occur through proton-assisted dissociation. [ABSTRACT FROM AUTHOR]

Highly efficient magnetic resonance imaging (MRI) probes have been prepared by loading GdIII complexes on the surface of solid lipid nanoparticles (pSLNs). Applicability as molecular imaging probes is demonstrated by an in vitro model study with targeted pSLNs. [ABSTRACT FROM AUTHOR]

The optimization of the physico-chemical properties of both GdIII chelates and nanocarriers is of great importance for the development of effective nanosystems for magnetic resonance imaging (MRI) applications. With this aim, macrocyclic GdIII chelates were selectively attached to the pendant amino groups exposed to the external surface of spheroidal mesoporous silica nanoparticles (MSNs). This was achieved by treating the metal complexes with MSNs that contained the templating surfactant molecules confined within the silica channels (hexadecyltrimethylammonium (CTA)/MSN), followed by extraction of the surfactant. The nanoparticles showed greatly improved 1H relaxometric efficiency relative to corresponding systems that also feature GdIII chelates conjugated inside the pores. A further significant relaxivity enhancement was observed after chemical transformation of the free amino groups into amides. The ionic relaxivity of the final nanoparticles ( r1p=79.1 m M−1 s−1; 0.5 T, 310 K) is one of the highest reported so far. [ABSTRACT FROM AUTHOR]