Elementos de realidad Aumentada

Magnetic nanoparticles can be coated with many types of inorganic materials including silica,109 noble metal110 and graphitic carbon.111 Not only are these materials generating repulsive force (Columbic force, steric repulsion) to stabilize nanoparticles in various solvents, they also form an inert shell to protect the inner core materials from degradation and prevent the releasing of toxic ion simultaneously. Additionally, these inorganic materials are also capable to react or interact with many bio-related molecules, and are available for further modification to design and fabricate functional materials for biomedical applications.

1.3.3.1. Silica

Silica is widely used as coating material for magnetic nanoparticles because it is biocompatible, resistant to degradation and their surface enriched silanol group are readily available for functionalization to covalently couple various biomolecules for different biomedical applications.109,112,113 As we know, both van der Waals forces and magnetic dipole forces are responsible for the aggregation of magnetic nanomaterials. Growing a silica layer can not only increase the inter-particle distance to reduce short-range van der Waals attraction, but shield the magnetic dipole interaction as well.8 Additionally, the negatively charged silica surface generates coulomb repulsion to effectively enhance the inter-particle spacing. If silica is further

functionalized with other functional silane such as APTES, the surface can also be positively charged.

Silica coating on magnetic nanoparticles are usually realized in three different routes. The first is basically exploited from the well-know Stöber method.113-115 Water-soluble magnetic nanoparticles prepared by co-precipitation or other method are dispersed in water or a mixture of water and alcohol where silica precursor such as TEOS hydrolyze and condense in-situ on the surface of nanoparticle and form a silica layer with controllable thickness. Micelle or reverse-micelle based on microemulsion synthesis is another promising approach to generate silica coating.112,116,117 In a water-in oil system, nonionic surfactant (e.g. Ig-CO520) stabilize small water droplet in a continuous oil phase (e.g. cyclohexane). These reverse-micelles confine the hydrolysis of silica precursors and control the coating process, resulting in very uniform silica layer. The disadvantage of this pathway is also obvious. Because micelles are formed as nanoreactors, much effort is required to purify the product from the solvents and remove large amount of surfactant after the coating. The third one, silane exchange or silanization approach,118,119 which is first developed for QDs,120 is less popular than in-situ coating method and microemulsion method. However, it is very effective in generating ultra-thin silica layer. In a typical procedure, as-prepared hydrophobic Fe3O4 nanoparticles are dispersed in nonpolar

solvents (e.g. toluene) and simply mixed with silane under heating until complete precipitation, producing readily water-soluble silica coated Fe3O4 nanoparticles. Because silane molecules can

bear many types of head-group, applying different silane during the coating can easily decorate the surface with desired functionalities.

In Stöber and microemulsion coating methods, surface functionalizations are usually performed on silica shell to improve its reactivity and availability toward the conjugation with biomolecules. This modification can be achieved by refluxing silica coated nanoparticles with functional silane molecules in alcohol or other solvents.114,117 The surface silanol groups react with silane and form a stable crosslinked network that imparts water-solubility and reactivity to the nanoparticles simultaneously. Instead of post-synthetic immobilization, desired functionality

can be incorporated during the growing of silica layer by a co-condensation of silica precursors with functional silane.121-123 Thus, multiple steps and repeated purification can be avoided.

1.3.3.2. Nobel Metal

The application of iron oxide magnetic nanoparticles (magnetite-Fe3O4,

γ-maghemite-Fe2O3), especially Fe3O4 nanoparticles is hindered by the oxidizable surface in

complicate physiological environment, which induce degradation and cause release of toxic ions.110 In order to protect their applicability, gold is widely used to coat these magnetic nanoparticles to enhance their stability and resistant to biodegradation. Additionally, the surface chemistry of gold particles is well studied and their high reactivity toward thiolated organic molecules will compensate for the lack of surface tunable ability of magnetic particles.124 Furthermore, gold possess unique shape and structure depended optical properties (absorbing near infrared light), which are highly desired for diagnostic and therapy.125,126

Similar as in silica coating, the deposition of Au can also be achieved in both aqueous phase and non-polar organic phase. By simply mixing water-soluble magnetic nanoparticles and Au precursors such as HAuCl4 in water, followed with addition of reducing agents (e.g. NaBH4), Au

layer with controllable thickness can be obtained.110,127 If magnetic nanoparticles are stabilized with organic ligand with terminal amine or thiol groups, the coating efficiency would be improved because of the favorable affinity of amine of thiol with noble metals. Xie128 and coworker introduce another two steps method to prepare Fe3O4/Au core/shell nanoparticles, in

which small gold nanocrystals were first attached onto polyethyleneimine stabilized nanoparticles as seeds. Then, more Au precursors and reducing agents are added to form a monolayer of gold. When hydrophobic nanoparticles are used and coating was performed in non-polar solvents, the same microemulsion approach for generating silica layer is applicable to Au. Besides reverse micelle method, Zhong129,130 et al. demonstrated a novel method for the formation of the gold shell at the iron oxide nanocrystal cores with high monodispersity and controllable thickness. The Fe3O4 nanoparticles were first synthesized via thermal decomposition

method. Next, without purification, the reactions solution is mixed with Au precursors, Au(OOCCH3)3, in which gold is deposited onto Fe3O4 via reduction of precursors.

1.4. Bioapplications of Iron Oxide Magnetic Nanoparticles

Iron oxide magnetic nanoparticles have been extensively studied for their potentials in various clinic areas. Their powerful magnetic properties have attracted great interests in developing next generation contrast agents for MRI. The very low cytotoxicity largely eliminates the safety concern about in vivo utilization that exists in many other nanomaterials (i.e. quantum dots). Small iron oxide nanoparticles (below 20 nm) that exhibit superparamagnetic behavior have demonstrated their ability in effective separation of many biomolecules or cells. Their large surface areas enable very high density of conjugation with desired drug or biomolecules, leading to outstanding performance on different applications.