Magnetic Nanoparticles in Human Health and Medicine

However, this process provides to material design new tools for a bottom‐up approach. In this context, the clustering of the nanoparticles can be induced and guided from internal and external forces, which utilizes van der Waals forces, magnetic and electrostatic interactions e molecular interactions. In all, by combining these different modes, it was shown how the strength of the assembly of nanoparticles increased.

All the contributions considered in this chapter pointed out that the clustering of magnetic nanoparticles certainly offers numerous advantages compared to individual nanoparticles. A point to be taken into consideration for the design of these nanostructures is certainly the planned application for the nanocomposite. It is complicated for a nanostructure to simultaneously meet the requirements of MRI or MPI in the diagnostic field, magnetic hyperthermia, or drug delivery in the therapeutic field. Taking into account the specific application, for the magnetic separation of analytes, the size of the nanocluster is undoubtedly not a limitation, it is instead essential that the clusters respond very quickly to the magnetic field, that they are stable/reusable and that the attraction to the magnet is complete. The overall size takes on particular importance only in case the nanoclusters have to be uptaken by the cells that had to be separated. In this case, superordinate structures, or obtained by direct synthesis, even of submicrometric dimensions are to be favored as they respond more to the applied magnetic field.

Concerning magnetic resonance imaging, on the other hand, it is very important to guarantee to magnetic nanoparticles surface complete access to the protons of the water molecules in the tissues, to generate a correct interference induced by the magnetic field applied during the measurement. The best nanostructures that offered a higher relaxivity than the starting nanoparticles are those that involved the use of porous coatings; also, a very ordered clustering that supports the dipole–dipole interaction between the nanoparticles in the cluster generates an increase in relaxivity r 2.

Magnetic hyperthermia is probably the application that is most affected by the clustering process of the nanoparticles because some of the phenomena that guarantee the increase in temperature in the presence of an alternating magnetic field are suppressed. In particular, this phenomenon concerns Brownian relaxation: the nanoparticles, being blocked in a dense core by the shell that protects the cluster and by interparticle interactions, have no possibility of rotating inside the fluid. This also happens for those agents in which the main cause of hyperthermia is considered hysteresis losses. Very small clusters of nanoparticles, even in 2D, can preserve high SAR values. Furthermore, the possibility of using biodegradable polymers, with the consequent release of the individual nanoparticles at the target site after structure decomposition, can help to recover those properties lost through the clustering process.

Regarding the in vivo applications of nanoclusters, it is essential to keep the dimensions below 100 nm to allow the nanodevice not to be sequestered quickly by the liver and spleen and, therefore, to reach the target site through extravasation. Furthermore, the possibility of grafting a coating that allows a specific functionalization and, therefore, a specific target recognition (avoiding a passive EPR distribution) in the tissues is certainly an added value for medical nanoclusters. On the other hand, magnetic targeting requires small nanoclusters, but at the same time, they must respond to an external magnetic field very strongly to be guided by an external magnetic field. The use of nanoclusters as a carrier for drug delivery must also take these considerations into account; in this case, the polymers that act as drug reservoirs could even affect the physical properties of the magnetic nanoparticles and limit further applications.

Probably, the only application that still does not have a clear response on the usefulness of clustering of nanoparticles is magnetic particle imaging (MPI). It is a fairly recent technique in which Ferucarbotran is still considered the standard. Theoretically, interparticle interactions limit the use of this technique for clusters. Still, recently the scientific community started to report about multicore nanoparticles or superferromagnetism in elongated oriented clusters (e.g. chain‐like structures) whose use in vivo must, however, overcome the in‐depth evaluation of biocompatibility and colloidal stability of structures (Bulte 2019).

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