Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging

Abstract

In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed.

Multi-functional liposomes having temperature-triggered release and magnetic resonance imaging for tumor-specific chemotherapy

“…The former can improve accumulation of the carriers in tumor tissues through the enhanced permeation and retention (EPR) effect [4,5] and the latter can increase therapeutic effect by releasing drug specifically at the diseased tissues upon application of stimuli to the target sites [6][7][8]. In addition, another important function for the improvement of accuracy of drug delivery might be imaging function of carriers [9][10][11][12][13][14]. If drug carriers have these functions and properties, efficient cancer chemotherapy can be achieved by following accumulation of carriers to the target sites and triggering drugs by stimuli application after the maximum acculturation of the carriers at the targets sites.…”

“…Based on these advantages of liposomes, many attempts have been made to provide MR imaging functions to them [14]. Considering that the liposome lumen must be used to encapsulate large amounts of drug molecules, the membrane moiety might be suitable for the incorporation of MRI probes.…”

Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity

“…However, the r 1 values measured for both the formulations were lower than the relaxivities typically displayed by liposomes incorporated with macrocyclic Gd(III) complexes (>10 s −1 mM −1 ). 23,24 This observation is not surprising because a deep structural investigation performed on a very close analogue of L outlined that this class of Gd-based SCA displays the isomerism commonly observed for macrocyclic lanthanide complexes, for which the coordination cage adopts two interconverting conformations based on square-or twisted-square antiprismatic structures (SAP and TSAP, respectively). 21,25 The peculiarity of this class of Ca-sensing SCAs is that the Gd(III) ion in the SAP isomer is fully coordinated by the ligand with seven donor atoms from the DO3A cage plus two donor groups (one amide and one carboxylate) from the EGTA-like cage.…”

Lipid-Based Nanoparticles in Cardiovascular Molecular Imaging

“…This drawback has to be overcome by designing suitable amplification procedures unusually based on the accumulation of the imaging agents at the targeting sites. [4] A general strategy for achieving this goal utilizes nanosized systems such as liposome, micelles, microemulsions, polymers etc…that are able to deliver a huge payload of Gd complexes [5][6]. The nanocarriers may be functionalized with suitable vectors that provide the overall particles with the required recognition capabilities towards the selected target.…”