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.

Amphiphilic Janus-dendrimers are able to self-assemble into nanosized vesicles named dendrimersomes. We recently synthesized the 3,5-C 12 -EG-(OH) 4 dendrimer that generates dendrimersomes with very promising safety and stability profiles, that can be loaded with different contrast agents for in vivo imaging. In this contribution, nanovesicles were loaded with both the Magnetic Resonance Imaging (MRI) reporter GdDOTAGA(C 18 ) 2 and the glucocorticoid drug Prednisolone Phosphate (PLP), in order to test their effective potential as theranostic nanocarriers on murine melanoma tumour models. The incorporation of GdDOTAGA(C 18 ) 2 into the membrane resulted in dendrimersomes with a high longitudinal relaxivity (r 1 = 39.1 mM -1 s -1 , at 310 K and 40MHz) so that, after intravenous administration, T 1 -weighted MRI showed a consistent contrast enhancement in the tumour area. Furthermore, the nanovesicles encapsulated PLP with good efficiency and displayed anti-tumour activity both in vitro and in vivo, thus enabling their practical use for biomedical theranostic applications.

One of the most challenging tasks of the cancer research is the enhancement of the amount of the chemotherapeutic agent that can reach the target site. To achieve this goal, nanovectors capable of encapsulating the drug and releasing it following a specific stimulus have been developed. In light of this, a key point is the necessity to monitor the effective drug release through a safe and highly performing imaging technology such as Magnetic Resonance Imaging (MRI). Liposomes are highly biocompatible nanovesicles that consist of bilayered phospholipid-based membrane encompassing an aqueous core. Almost 20 drug-loaded liposomes are currently approved for clinical use in USA and EU countries. If a liposomal nanomedicine is loaded with an MRI agent whose contrast is sensitive to the microenvironment and with a release kinetics similar to the co-transported drug, the system can act as an imaging reporter of drug release. This Perspective will offer a critical and brief overview of using MRI not only to verify and monitor the release process but also as a valuable tool to predict the therapeutic outcome. In particular, it will be presented representatives preclinical studies illustrating the in vivo potential of MRI-guided drug release protocols triggered by thermal and mechanical ultrasound-induced effects. Considering the therapeutic advantages of this approach, the possible benefits in reducing the side effects and the good results reported at preclinical level, there is a reasonable hope that the near future could witness the entrance in clinical routine of MRI-guided procedures supporting ultrasound-induced drug release protocols.