a Dendrimersomes are nanosized vesicles constituted by amphiphilic Janus dendrimers (JDs), which have been recently proposed as innovative nanocarriers for biomedical applications. Recently, we have demonstrated that dendrimersomes self-assembled from (3,5)12G1-PE-BMPA-G2-(OH) 8 dendrimers can be successfully loaded with hydrophilic and amphiphilic imaging contrast agents. Here, we present two newly synthesized low generation isomeric JDs: JDG0G1(3,5) and JDG0G1(3,4). Though less branched than the above-cited dendrimers, they retain the ability to form self-assembled, almost monodisperse vesicular nanoparticles. This contribution reports on the characterization of such nanovesicles loaded with the clinically approved MRI probe Gadoteridol and the comparison with the related nanoparticles assembled from more branched dendrimers. Special emphasis was given to the in vitro stability test of the systems in biologically relevant media, complemented by preliminary in vivo data about blood circulation lifetime collected from healthy mice. The results point to very promising safety and stability profiles of the nanovesicles, in particular for those made of JDG0G1(3,5), whose spontaneous self-organization in water gives rise to a homogeneous suspension. Importantly, the blood lifetimes of these systems are comparable to those of standard liposomes. By virtue of the reported results, the herein presented nanovesicles augur well for future use in a variety of biomedical applications.

A new class of nanovesicles formed by the self-assembly of amphiphilic Janus dendrimers, dendrimersomes, loaded with hydrophilic or amphiphilic magnetic resonance imaging chelates shows promising properties as a novel, efficient and versatile nanoplatform for biomedical imaging.

Perthiolated β-cyclodextrin-based nanocapsules incorporating diaquo Gd(III)-complexes represent a promising new type of bioresponsive MRI contrast agent, showing a pronounced relaxivity change upon degradation in a reducing environment.

High precision PET/CT imaging of solid tumors improves diagnostic credibility and clinical outcome of patients. An epitope of the oligomerization domain of Hsp70 is exclusively exposed on the membrane of a large variety of tumor types, but not on normal cells, and thus provides a universal tumor-specific target. Here we developed a novel PET tracer TPP-PEG-DFO[Zr] based on the tumor cell-penetrating peptide probe TPP, which specifically recognizes membrane Hsp70 (mHsp70) on tumor cells. The implemented PEG moiety supported tracer stability and improved biodistribution characteristics The of the tracer ranged in the low nanomolar range (18.9 ± 11.3 nmol/L). Fluorescein isothiocyanate (FITC)-labeled derivatives TPP-[FITC] and TPP-PEG-[FITC] revealed comparable and specific binding to mHsp70-positive 4T1, 4T1, a derivative of the 4T1 cell line sorted for high Hsp70 expression, and CT26 tumor cells, but not to mHsp70-negative normal fibroblasts. The rapid internalization kinetics of mHsp70 into the cytosol and the favorable biodistribution of the peptide-based tracer TPP-PEG-DFO[Zr] enabled a tumor-specific accumulation with a high tumor-to-background contrast and renal body clearance. The tumor-specific enrichment of the tracer in 4T1 (6.2 ± 1.1%ID/g), 4T1 (4.3 ± 0.7%ID/g), and CT26 (2.6 ± 0.6%ID/g) mouse tumors with very high, high, and intermediate mHsp70 densities, respectively, reflected mHsp70 expression profiles of the different tumor types, whereas benign mHsp70-negative fibroblastic hyperplasia showed no tracer accumulation (0.2 ± 0.03%ID/g). The ability of our chemically optimized peptide-based tracer TPP-PEG-DFO[Zr] to detect mHsp70 suggests its broad applicability in targeting and imaging with high specificity for any tumor type that exhibits surface expression of Hsp70. A novel peptide-based PET tracer against the oligomerization domain of Hsp70 has potential for universal tumor-specific imaging across many tumor type..

Three different tetraazamacrocyclic ligands containing four amide substituents that feature groups (namely allyl, styryl and propargyl groups) suitable for polymerisation have been synthesised. Gadolinium(III) complexes of these three ligands have been prepared as potential monomers for the synthesis of polymeric MRI contrast agents. To assess the potential of these monomers as MRI contrast agents, their relaxation enhancement properties and cytotoxicity have been determined. A europium(III) complex of one of these ligands (with propargyl substituents) is also presented together with its PARACEST properties. In addition, to gain further insight into the coordination chemistry of the tetra-propargyl substitited ligand, the corresponding zinc(II) and cadmium(II) complexes have been prepared.The X-ray crystal structures of the tetra-propargyl ligand and its corresponding gadolinium(III), zinc(II) and cadmium(II) complexes are also presented.