Nanostructured gadolinium(III) micelles: Synthesis, characterization, cytotoxic activities, and MRI applications in vivo

Gadolinium-based contrast agents (GBCAs) are used in around 40 % of MRI procedures. Despite initial perceptions of minimal risk, their long-term use has emphasized the need to reduce toxicity and develop more efficient GBCAs with extended blood retention. Advancements in nanomaterials have led to improved GBCAs, enhancing MRI diagnostics. This study synthesizes and characterizes nanostructured gadolinium(III) micelles as superior MRI contrast agents. The complexes, [Gd(L)2], where L is a ligand of the N-alkyl-N-methylglucamine surfactant series (L8, L10 or L12, L10), form nanostructured micelles in aqueous solution. Gd(L8)2 and Gd(L10)2 relaxivities remained stable across concentrations. Compared to Gd-DTPA, Gd(III) micelles showed enhanced T1-weighted MRI contrast. Gd(L12)2 micelles exhibited cytotoxicity against B16F10 melanoma cells (IC50 42.5 ± 2.2 μM) and L292L929 fibroblasts (IC50 52.0 ± 2.5 μM), with a selectivity index of 1.2. In vivo application in mice brain T2-weighted images suggests nanostructured Gd(III) micelles are promising MRI contrast agents for targeting healthy organs or tumors. Gadolinium(III) micelles with alkyl-N-methylglucamine surfactant series were synthesized. Gd(III) micelles were highly active against B16F10 murine metastatic melanoma cell line and non-toxic towards L292 murine fibroblasts. The nanostructured Gd(III) micelles were found to be potentially prominent MRI contrast agent in in vivo model. [Display omitted] •Synthesis of gadolinium(III) micelles with alkyl-N-methylglucamine surfactant series•Gd(III) micelles outperforms Magnevist® in relaxivity values•Gd(III) micelles offers superior MRI potential over Magnevist®•Gd(III) micelles showed no toxic effects against murine fibroblasts•Gd(L12)2 and Gd(L10)2 displayed higher antitumor potential than reference drug