MAGNETIC PROPERTIES OF NOVEL NANOSTRUCTURED MATERIALS: FUNDAMENTAL ASPECTS AND BIOMEDICAL APPLICATIONS TOWARD THERANOSTICS
Creators: name: AMIRI DOUMARI, HOUSHANG
Publisher: name: Universit� degli Studi di Milano
Year: 2010

description: The SPIONs are currently commercially produced. Endorem� (by Guerbet Group, Feridex in the USA) is one of the most known commercial MRI contrast agents and it is constituted by a magnetic core (diameter ~6?7nm) of mixed ?-Fe2O3 and Fe3O4 oxides coated with dextran, giving a nanoparticle which has an average ~150 nm hydrodynamic diameter. Despite the undoubtful efficacy of Endorem�, problems of reproducibility of the MR images are often encountered, possibly because the nanoparticles present high polydispersity and different batches of sample possess different mix of the two iron oxides. The limited reproducibility together with the necessity of obtaining systems with better controlled microscopic properties, have motivated many research groups to synthesize new monodispersed SPIONs families. 
The central idea of the research activity reported in the thesis has been the study of novel magnetic nanoparticles (MNP) for application as contrast agent (CA) in MRI and future other diagnostics and therapeutics, such as optical imaging, targeted drug delivery, and magnetic hyperthermia. A second part of research was related to fundamental aspects of magnetism, in which the spin dynamics and magnetic properties of molecular nanomagnets were studied. Concerning the second part of research we have just reported the related publications in the Appendix B while in the main body of the thesis we will focus on the application part of the research, i.e. biomedical applications of MNPs.
To test the efficiency of new samples in contrasting the MR images, we have investigated magnetic and relaxometric properties of two different types of novel superparamagnetics nanoparticles:

1. Polymer-based nanostructured bio-ferrofluids. These materials, in brief bio-ferrofluids, are candidates for the hyperthermia, optical imaging, and MRI. Bio-ferrofluids are a series of novel maghemite/polymer composite ferrofluids with variable magnetic core size. Our investigations have shown that they have a good efficiency as MRI CAs. These biocompatible ferrofluids, which contain anchoring groups for bio-functionalization, can incorporate fluorescent dyes and have shown low cellular toxicity in previous studies. Therefore, they can be proposed as possible platforms for multifunctional biomedical applications. The NMRD profiles showed that the efficiency parameter, i.e. the nuclear transverse relaxivity r2 , for particles with sizes greater than 10nm assumes values comparable with or better than the ones of commercial samples. The best results have been obtained in particles with the biggest magnetic core. The MRI in-vitro experiments, at ?=8.5MHz, using the gradient-echo and spin-echo sequences have confirmed the NMRD results, thus allowing us to suggest these superparamagnetic nanoparticles as novel multifunctional materials.

2. Superparamagnetic colloidal nano-crystal clusters. These compounds are candidates for the targeted drug delivery and MRI. They are a novel class of superparamagnetic colloidal nano-crystal clusters (CNCs) coated with different bio-compatible coatings such as polyethylene glycol fumarate (PEGF). We have investigated cell endocytosis, drug release, NMR relaxometry and in vitro MRI of CNCs with various biocompatible coatings. It is shown that the transverse relaxivity r2 for the PVA-coated, PEGF-coated, and crosslinked PEGF-coated CNCs is efficient enough to contrast suitably the magnetic resonance images. The same samples have shown a good ability also in controlled drug releasing (particularly the crosslinked PEGF-coated compound), thus finally allowing us to propose this class of compounds for future applications in theranostics, i.e., therapy and diagnostics with the same compound. 
 By means of the work done in this thesis, we were able to conclude that both classes of compounds investigated can be proposed as novel theranostic, i.e. therapy and diagnostics with the same compound, agents.