New SubmissionInvestigation of Lipid-Based Liquid Crystal Phase Behavior and Tuning Water Channel Sizes for Enhanced MRI Contrast Agents

Incorporating chelating lipids into lipid matrices represents a promising approach for designing molecular assemblies with potential applications in biomedical imaging, particularly as Magnetic Resonance Imaging (MRI) contrast agents. Works of others showed high molecular weight amphiphiles, such as Gd-chelating lipids, have demonstrated enhanced relaxivity (r1) due to prolonged molecular reorientation times (τr) and reorientation correlation times (τc) [1]. Building upon this, this study explores the integration of DTPA (diethylenetriaminepentaacetic acid) chelates, with and without Gd metal ion, into a lipid mixture of glyceryl monooleate (MO) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). Specifically we show how the incorporation of DTPA chelates within the MO and DOPC matrix influences lipid phase behavior, molecular dynamics, and relaxometric properties, thus evaluating their potential impact on the development of MRI contrast agents. The nanoassemblies were characterized through a range of techniques, including Nuclear Magnetic Resonance (NMR) methods—1H NMR and NMR relaxometry— Dynamic Light Scattering (DLS) and Cryogenic Transmission Electron Microscopy (cryo-TEM) along with Small Angle X-ray Scattering (SAXS) to determine water channel diameters within the different lipid phases [2]. This structural information is critical for understanding how the size and arrangement of water channels can influence Chemical-Exchange Saturation Transfer (CEST) effects and water relaxation dynamics, both of which are pivotal in enhancing the contrast efficiency of MRI agents.