Peptide materials based on the aggregation of poly-phenylalanine conjugates containing gadolinium complexes and acting as potential contrast agents (CAs) in Magnetic Resonance Imaging (MRI) are described. Monomers contain two (F2) or four (F4) phenylalanine residues for self-assembly, a chelating agent, DOTA or DTPA, for achieving gadolinium coordination and ethoxylic linkers at two (L2) or six (L6) PEG units between the chelating group and peptide region. Both DOTA and DTPA tetra-phenylalanine derivatives, and their gadolinium complexes DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4, are able to self-aggregate at very low concentration. Structural characterization, obtained by CD and IR measurements, confirms the amyloid type fibril formation in which an antiparallel peptide alignment is preferred. Amyloid type fibril formation was also observed, in solid state, by TEM images and X-ray diffraction patterns. The relaxivity values of DOTA(Gd)-L6-F4 and DTPA(Gd)-L6-F4 and their ability to enhance the MRI cellular response on J774A.1 mouse macrophages cell line indicate that these peptide materials are promising candidate as a new class of supramolecular gadolinium based MRI contrast agents

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A novel class of paramagnetic liposome-based systems acting as dual T(1) and CEST (1)H-MRI contrast agents is described. The vesicles contain a shift reagent in the aqueous core and a Gd-complex on the external surface conjugated through a biodegradable linker. As such, the probe can generate T(1) contrast only, but after the cleavage and removal of the Gd-coating, the CEST contrast is switched on.

Abstract:A novel fluorescein/Gd-DOTAGA containing nanoprobe for tumor visualization by Optical

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The development of nanomedicines in cancer therapy is constantly growing because of the advantages associated with the use of nanosized drug delivery systems. Among them, the possibility of accurate spatiotemporal control of the release of the chemotherapeutic from the carrier is one of the most interesting and clinically relevant. To further improve the therapy outcome, the clinical translation of imaging protocols for the in vivo visualization of the release step is of paramount importance. In this work, the combination of the great chemical versatility of liposomes and the outstanding potential of MRI chemical exchange saturation transfer agents has been successfully harnessed to image the selective release of the liposomal content stimulated by endogenous (variation of pH) and externally applied (nonfocused ultrasound) stimuli. The use of clinically safe components (both liposomes and MRI agents) and the good results obtained in vitro hold promise for a successful future in vivo translation.

The accurate characterization and description of the vascular network of a cancer lesion is of paramount importance in clinical practice and cancer research in order to improve diagnostic accuracy or to assess the effectiveness of a treatment. The aim of this study was to show the effectiveness of liposomes as an ultrasound contrast agent to describe the 3-D vascular architecture of a tumor. Eight C57BL/6 mice grafted with syngeneic B16-F10 murine melanoma cells were injected with a bolus of 1,2-Distearoyl-sn-glycero-3-phosphocoline (DSPC)-based non-targeted liposomes and with a bolus of microbubbles. 3-D contrast-enhanced images of the tumor lesions were acquired in three conditions: pre-contrast, after the injection of microbubbles, and after the injection of liposomes. By using a previously developed reconstruction and characterization image processing technique, we obtained the 3-D representation of the vascular architecture in these three conditions. Six descriptive parameters of these networks were also computed: the number of vascular trees (NT), the vascular density (VD), the number of branches, the 2-D curvature measure, the number of vascular flexes of the vessels, and the 3-D curvature. Results showed that all the vascular descriptors obtained by liposome-based images were statistically equal to those obtained by using microbubbles, except the VD which was found to be lower for liposome images. All the six descriptors computed in pre-contrast conditions had values that were statistically lower than those computed in presence of contrast, both for liposomes and microbubbles. Liposomes have already been used in cancer therapy for the selective ultrasound-mediated delivery of drugs. This work demonstrated their effectiveness also as vascular diagnostic contrast agents, therefore proving that liposomes can be used as efficient “theranostic” (i.e. therapeutic + diagnostic) ultrasound probes.

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