Paramagnetic Liposomes as Innovative Contrast Agents for Magnetic Resonance (MR) Molecular Imaging Applications

Abstract

This article illustrates some innovative applications of liposomes loaded with paramagnetic lanthanide-based complexes in MR molecular imaging field. When a relatively high amount of a Gd(III) chelate is encapsulated in the vesicle, the nanosystem can simultaneously affect both the longitudinal (R(1)) and the transverse (R(2)) relaxation rate of the bulk H2O H-atoms, and this finding can be exploited to design improved thermosensitive liposomes whose MRI response is not longer dependent on the concentration of the probe. The observation that the liposome compartmentalization of a paramagnetic Ln(III) complex induce a significant R(2) enhancement, primarily caused by magnetic susceptibility effects, prompted us to test the potential of such agents in cell-targeting MR experiments. The results obtained indicated that these nanoprobes may have a great potential for the MR visualization of cellular targets (like the glutamine membrane transporters) overexpressing in tumor cells. Liposomes loaded with paramagnetic complexes acting as NMR shift reagents have been recently proposed as highly sensitive CEST MRI agents. The main peculiarity of CEST probes is to allow the MR visualization of different agents present in the same region of interest, and this article provides an illustrative example of the in vivo potential of liposome-based CEST agents.

Proton Chemical Exchange Saturation Transfer (CEST) MRS and MRI

“…Three recent dedicated CEST workshops (3rd, 4th, and 5th international CEST workshops in Annapolis, 2012, Torino, 2014, and Philadelphia 2016) drew about 90-200 registrants. The last decade has shown major developments for paraCEST agents, 14,15,20,89,90,119,[135][136][137][138][139][140][141][142][143][144][145][146][147][148] diaCEST agents, 12,13,17,42,43,68,72,88,102,116,125,128,[149][150][151][152][153][154][155][156][157][158][159][160] and even hyperpolarized (hyperCEST) agents. 161,162 This is not surprising in view of the number of potential applications including pH imaging, metabolite detection, ion detection, cellular protein and peptide imaging, cell labeling, temperature i...…”

“…161,162 This is not surprising in view of the number of potential applications including pH imaging, metabolite detection, ion detection, cellular protein and peptide imaging, cell labeling, temperature imaging, detection of enzyme activity, CEST reporter genes, and the imaging of sugars. Another important development is the use of CEST agents in liposomes (lipoCEST) 142,143 to detect picomolar concentrations of these nanoparticles via the exchange of water between intra-and extraliposomal environments. 16,142,143,163,164 While the paraCEST, lipoCEST, and hyperCEST agents show much potential, due to space limitations this remaining section will focus on some of the diaCEST applications that have actually been applied in humans.…”

“…Another important development is the use of CEST agents in liposomes (lipoCEST) 142,143 to detect picomolar concentrations of these nanoparticles via the exchange of water between intra-and extraliposomal environments. 16,142,143,163,164 While the paraCEST, lipoCEST, and hyperCEST agents show much potential, due to space limitations this remaining section will focus on some of the diaCEST applications that have actually been applied in humans.…”

Multinuclear magnetic resonance evaluation of tumor tissue

“…The detection threshold for the visualization of a 19 F signal from PFCs in a biological specimen has been estimated to be quite high (ca. 0.1 M at 4.7 T) and it is possible to detect up to nanomolar concentrations of PFCs (Srinivas et al, 2007;Terreno et al, 2008). PFCs are suitable compounds for cell or drug labeling with 19 F nuclei.…”

Nanotechnologies for Curcumin: An Ancient Puzzler Meets Modern Solutions

“…Possessing the advantages of high biocompatibility, easy preparation, chemical versatility, and simple modulation of their pharmacokinetic properties by changing the chemical composition of the bilayer components, liposomes as a drug delivery system have been used to improve the therapeutic activity and safety of drugs for many years [20].…”