Well-Defined, Multifunctional Nanostructures of a Paramagnetic Lipid and a Lipopeptide for Macrophage Imaging

Abstract

In the field of nanomedicine there is a great demand for technologies that allow the creation of self-assembled structures of which the size and morphology can be accurately controlled. In the current study, we report a nanoparticle platform that is composed of a paramagnetic lipid and a fluorescently labeled lipopeptide. By judiciously controlling the ratio of the aforementioned amphiphilic molecules a variety of well-defined nano-sized supramolecular structures with different sizes and morphologies could be created. The hydrodynamic radii of the different structures were determined by dynamic light scattering. Cryo-TEM revealed the aggregate morphology to vary from small micellar structures to plate-like and even full grown ribbons of which the aspect ratios varied from a diameter of 5–8 nm to structures with a width of up to 25 nm and infinite length. Interestingly, nuclear magnetic resonance dispersion profiling revealed excellent properties for MRI and also showed that the relaxivity of the structures was tunable and morphology dependent. Finally, macrophage cells were treated with two selected nanoparticles and were shown to be avidly taken up. In conclusion we demonstrate a methodology to create structures that are (1) paramagnetic to enable their detection with MRI, (2) exhibit fluorescent properties, (3) can be tuned to defined sizes and shapes and (4) are efficiently taken up by macrophage cells in vitro.

Multimodality Imaging Probes: Design and Challenges

“…A number of groups have reported synthesis of liposomes containing a rhodamine phosphotidylethanolamine derivative and a homemade Gd–lipid for bimodal MR and fluorescence imaging 43–45. Two groups report the use of Gd–chelate–bis(stearylamide), either purchased commercially45,46 or synthesized in house 43.…”

“…Two groups report the use of Gd–chelate–bis(stearylamide), either purchased commercially45,46 or synthesized in house 43. For the latter group, the development of Gd–DOTA–DSA, Gd(III) 2-{4,7-bis-carboxymethyl-10-[ N , N -distearylamidomethyl- N ′-amidomethyl]-1,4,7,10-tetraazacylclododec-1-yl}acetic acid, followed on their work in which they coupled Gd–DOTA to cholesterol for incorporation to liposomes 47.…”

Hybrid magnetic nanostructures (MNS) for magnetic resonance imaging applications

“…Bimodal Optical/T 1 lipid nanoparticles consist of lipid functionalized with Gd chelate and fluorescent molecule. The most common bimodal lipids are a combination of either Gd or Mn chelate with rhodamine as a fluorophore (Gd/Mn-Rh-Lipid NP) [110–113]. Gd-Rh-Lipid NP was applied in vivo for tracking tumor cells at cellular scale by optical imaging in addition to anatomical information from T 1 weighted MRI.…”

TEM and Associated Techniques

“…Nevertheless, assuming that the transfer suspension is dilute enough, a TEM session would yield an adequate number of images for a proper particle distribution analysis, and a diligent researcher would receive a visual feedback for the materials synthesis and specimen preparation. However, when evaluating the synthetic protocol, one should be so careful as not to propose the reaction schematics based entirely on the shapes observed with the TEM, as the obtained information might prove insufficient to define the actual processes taking place during the reaction [6,22,[44][45][46][47]. As the details tying the pieces of the proposed schematics are lacking, overreliance on the static images for reconstructing the entire reaction pathway could lead to erroneous conclusions [22,.…”