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3 Clustering of Magnetic Nanoparticles for Nanomedicine
Giacomo Mandriota1 and Riccardo Di Corato2
1 Istituto Italiano di Tecnologia, via Morego, Genoa, Italy
2 Institute for Microelectronics and Microsystems (IMM), CNR, Via Monteroni, Lecce, Italy
3.1 Introduction
The use of magnetic nanoparticles has been the subject of great interest for their use in various applications such as the high‐density storage of data (Weller and Doerner 2000), magnetic energy (Zeng et al. 2002), magnetic separations (Hahn et al. 2007), drug delivery (Pulfer et al. 1999), and hyperthermia treatments (Jordan et al. 1999).
The peculiar properties of these nanoparticles have allowed developing remarkable multifunctional systems in nanomedicine. In particular, the possibility to temporarily magnetize the nanomaterial, when an external magnetic field is applied, allows obtaining a device that can be remotely activated and on‐demand. Obviously, even the individual nanoparticles have some limitations, such as the low concentration that is usually achieved at the target site when administrated into the bloodstream. Furthermore, these nanoparticles are perfectly stable from the colloidal point of view, but since the magnetization associated with the single nanoparticle is very low, they behave like a ferrofluid; therefore, it is difficult, or better impossible, to separate them from a suspension or to guide them inside a vessel by the magnetic field. To overcome these and other inherent limitations, one possibility is represented by the clustering of magnetic nanoparticles in colloidal assemblies. When the nanoparticles are inserted into a super‐structure, specific forces are activated or enhanced, which allow arising different properties compared to the single nanoparticles (but limiting, in certain cases, the advantages of the individual ones).
The assembly (Whitesides and Grzybowski 2002; Fialkowski et al. 2006) is undoubtedly a highly exciting process due to the evolution of the individual nanostructure into higher‐ordered nanostructures. The assembling application is realized in several fields, as systems serving as ultrasensitive biosensors (Service 2003), highly conductive nanowires of uniform‐width (Yan et al. 2003), ordered two dimensional (2D) nanoparticle arrays exhibiting unique electronic properties (Dorogi et al. 1995; Murray et al. 2000; Hecht 2005; Shevchenko et al. 2006), and materials of overall macroscopic dimensions and showing unusual bulk properties.
In this chapter, different aspects of nanoparticle clustering, with particular emphasis on magnetic ones and on the possible use in the field of nanomedicine, are discussed. Within this scenario, all the forces that govern at the nanoscale the generation of organized clusters of nanoparticles, and the balance between the different components able to control the formation of regular and functional structures, are initially analyzed. Then, in a more applicative section, some examples of magnetic nanoclusters that have biomedical relevance are highlighted; the shown nanocomposites are classified according to the type of preparation and/or the type of molecule (e.g. polymers, polysaccharides) which has been used to control and stabilize the obtained cluster. Finally, some studies that resulted in the use of magnetic clusters to the animal study, applying a theranostic approach, are commented in more detail. The purpose of this chapter is mainly to provide to the reader the bases for evaluating the advantages deriving from nanoparticle clustering and to report the most recent studies with relevance in the biomedical field, thus trying to illustrate the advantages of single techniques used.
3.2 Clustering Theory
To obtain the nanostructures assembly, it needs, if not fundamental, to understand and engineer the interactions between nanoparticles evolving them into desired structures. The components and the interactions lead to the formation of equilibrium structures, which are reached when the appropriate thermodynamic potential, as the free energies of Gibbs or Helmotz, is low. Moreover, it is not simple to obtain equilibrium conditions (Durbin and Feher 1996; Chayen 2002) and even more difficult if not impossible for the competitive gels or glasses formation (Dawson 2002; Foffi et al. 2002; Sciortino and Tartaglia 2005).
To get the assembling mechanism, it is fundamental that the nanoparticles organize themselves into ordered and macroscopic structures through direct interactions, such as interparticle forces, and indirect interactions, such as an external field.
The assembling mechanism relies on the colloidal interaction between the nanoparticles which organize themselves into ordered and macroscopic structures. The colloidal interaction represented the basis of the balance generated between the individual nanoparticles. These colloidal forces are based on a thermodynamic equilibrium treatment of the nanoparticle interactions. By considering a system where no external forces are