This study shows that the gelation process determines the size and phase of the nanoparticles formed in the silica matrix. The presence of polyol ligands on the surface of magnetite nanoparticles is confirmed by TGA measurement and FTIR analysis.
Polymer Stabilizers
Kumagai et al.480 reported a simple route for the synthesis of PEG-coated iron oxide nanoparticles by hydrolysis of FeCl3·6H2O in water and subsequent treatment with poly(ethylene glycol)-poly(aspartic acid) block copolymer. Microspheres composed of superparamagnetic iron oxide nanoparticles and chitosan have been developed as a novel MRI-detectable embolic material.
Other Strategies for Stabilization
Arabinogalactan-coated iron oxide nanoparticles are recognized by the asialoglycoprotein receptors they present on normal hepatocytes.416–420 PAA coatings increase the stability and biocompatibility of the particles and also aid in bioadhesion.421. To optimize the composite nanoparticles, the experimental parameters were varied and the properties of the resulting nanosystems were determined.
Methods of Vectorization of the Particles
The vector SPDP was obtained by reacting SPDP with the amino function of the vector. Particles with ω-hydroxyl or primary amine groups were prepared by reaction of the surface with alkylalkyloxysilane compounds [Si(OEt)3(CH2)3-.
Structural and Physicochemical Characterization
Size, Polydispersity, Shape, and Surface Characterization
First, it can define different parts of the nanoparticle: the crystalline part of the core, the whole iron core (crystalline and amorphous), the core, the shell and the hydrated layer, or even a meaningless geometric size in the particle. but only a physical sense. Particle core size can be determined from TEM images.530–533 This technique reports the total core particle size (crystalline and amorphous parts) and gives access to a number-weighted average value (Figure 7). Additionally, sample preparation may promote colloid aggregation and TEM measurements may not reflect the size and distribution in solution.
SANS is a powerful technique to obtain information on the size, polydispersity, shape (form factor), and even the structure of nanoparticles.551 The peculiarity of neutrons is that they interact with the nuclei of atoms present in the sample. This can be used to independently study the core and shell size of nanoparticles. Determining the diffusion coefficient of nanoparticles in solution gives access to the hydrodynamic radius of a corresponding sphere and the polydispersity of the colloidal solution.552 This radius is an intensity-weighted average value.
A correct conversion to a number or volume-weighted mean value requires knowledge of the complex refractive index. If the field is suppressed, the magnetic nanoparticles are randomly disoriented and the magneto-optical birefringence relaxes with a characteristic time related to the rotational diffusion time of the particles, giving access to the hydrodynamic radius. These techniques have been reviewed very recently.550 It is worth noting that all these techniques are used to describe the nature and strength of the bond between the iron oxide surface and the coating, but they are also used to understand the influence of the coating on the magnetic properties of.
Structure of Ferro- or Ferrimagnetic Nanoparticles
The anisotropy energy also determines the Neel relaxation time, which is another important parameter for the magnetic behavior of a single nanodomain particle. For dry powder of monodomain particles, the Neel relaxation time is characterized by the time constant of the return to equilibrium of the magnetization after a perturbation. The Ne'el relaxation then defines the fluctuations arising from the jumps of the magnetic moment between different easy directions.
The function that gives the evolution of the Ne´el relaxation timeτNwith the anisotropy energyEa is the product of two factors. Contrary to the exponential factor, τo(Ea) decreases as the value of the anisotropy energy increases. Under these conditions, the return of the magnetization to equilibrium is determined by two different processes.
The first is Ne´el relaxation, and the second is Brownian relaxation, which characterizes the viscous rotation of the entire particle (Figures 9 and 10). Evolution of the two components of magnetic relaxation with magnetite crystal radius (after Rosensweig662). The degree of particle aggregation should also strongly influence the Ne´el relaxation due to the dipolar intercrystalline coupling aspect of the anisotropy.
Use of Nanoparticles as Contrast Agents for MRI
For large particles, τB is shorter than τN because the Brownian component of the magnetic relaxation is proportional to the crystal volume and the Neel relaxation is an exponential function of volume. This relaxation is due to the movement of water protons near the local magnetic field gradients created by the paramagnetic ion. In contrast, in small crystals, the anisotropy energy is comparable to the thermal energy, so the probability that the magnetic moment points in a direction away.
The explanation of the field dependence of the longitudinal relaxation rate (NMRD profile) is in any case based on the so-called Curie relaxation,572 which arises from the separate consideration of two contributions to relaxation: firstly, diffusion to the inhomogeneous non-fluctuating magnetic field created by the average crystal. moment, in line with Bo (strictly speaking, this contribution is precisely called the Curie relaxation), and secondly, the fluctuations of the electronic magnetic moment or the Ne'el relaxation. When the anisotropy energy is large enough, it prevents any precession of the magnetic moment of superparamagnetic crystals. The magnetic fluctuations then arise from the jumps of the moment between different easy directions.
Fits to the simplified model of the NMRD profile for an endorem solution (a typical SPIO sample) and a MION46 solution (USPIO sample). The absence or presence of a dispersion at low fields provides information about the magnitude of the anisotropy energy. Let us focus on the first effect that allows control of the aggregation stage of the ferrofluid.
Applications
- MRI: Cellular Labeling, Molecular Imaging (Inflammation, Apoptose, etc.)
- In Vitro Bioseparation
- Drug Delivery
- Hyperthermia
It is characterized by a long correlation time, due to its large size, so that it mainly affects the secular term of the relaxation rate. The apparent dissociation constants (Kd./) of the three contrast agents were estimated from the MRI measurement. The results suggest that nanoparticles could be targeted to the cell surface markers expressed in tumor cells, at least in the case where the nanoparticles and the tumor model have characteristics similar to those of the BT-20 tumor.
Experiments can be performed in cloudy media and whole cell lysates, and the assay does not require immobilization of the target. After administration, larger particles with a diameter higher than 200 nm are readily sequestered by the spleen and eventually removed by the cells of the phagocytic system, resulting in decreased blood. It is expressed in calories per kilogram and is proportional to the rate of temperature rise (∆T/∆t) (Eq. 35).
The expression (equation 36) shows that if the radiation magnetic field is uniform, SAR depends only on the nature and volume fraction of superparamagnetic particles. The radiation frequency must be low enough to avoid an interaction of the electromagnetic field with the intracellular ions. Considering the evolution of τ with the crystal volume given by eqs 3, 5 and 6, Rosensweig662 has shown a very sharp SAR maximum for a diameter of about 14 nm in the case of magnetite.
Irradiating it by an oscillating wave of the magnetic field can increase the temperature and allow reaching the phase transition temperature of the liposome membrane. In conclusion, superparamagnetic colloids can be seen as a very promising agent for hyperthermia therapy, but this new field of application requires an improvement of reproducibility and size control during particle synthesis.
Conclusions and Perspectives
In his calculation, Rosensweig only took into account the bulk magnetocrystalline component of the anisotropy, but an evolution of the particle's aggregation stage should also cause a change of SAR due to the effect of dipolar intercrystal coupling on Ne´el relaxation times. Evaluation of the feasibility and survival benefit of this new hyperthermia approach is ongoing in animals, and the first clinical trials have recently been started.664,665 Ideally, the superparamagnetic crystals should be encapsulated with a drug in a liposome. The drug should then be massively and selectively released in the area exposed to the magnetic field.666.
This point seems crucial for optimizing the avidity for biological targets of targeted superparamagnetic nanoparticles based on the concept of multivalency.669 When the surface density of biovectors is variable, the avidity of targeted nanoparticles for their biological target can be increased. and consequently to modulate biological behavior. To this end, it is necessary to develop new precise analytical tools that can quantify the number of biovectors on the surface of nanoparticles. Much effort is needed to understand the interactions of nanoparticles with immune systems and to optimize the molecular interaction with conjugated receptor particles or ligandsinViVo.
For example, the optimization of the targeting activity should be systematically investigated by changing the flexibility and length of the linker between the surface and the biovectors to minimize interference of the coating with the binding. Additional preclinical and clinical studies in relevant animal models and disease states should be conducted to substantiate the proof-of-concept using various controls, especially in molecular MRI imaging. Finally, safety and biocompatibility studies, and especially long-term toxicity studies, should be conducted in addition to proof-of-concept studies.
Acknowledgments
Elsevier: Amsterdam, Netherlands, 1948. M.; Schertmann, U. Iron Oxides: Structure, Properties, Reactions, Occurrence and Uses; VCH Publishers: Weinheim, Germany, 1996. International Development Centre: Ottawa, Canada, 1997; Vol. 346) Hafeli, U.; Schu¨tt, W.; Teller, J.; Zbrorowski, M. Scientific and clinical applications of magnetic carriers;.
