Silica-coated Magnetic Nanoparticles

Nanotechnology is a scientific discipline involving multiple hard sciences such as chemistry, physic, biology, engineering, among others. The occurrence of novel properties when materials are reduced to nanosizes is the main reason for the scientific and technological interest in such discipline. In particular nanomedicine, that is nanotechnology applied to medicine, has suffered an exponential grow in the last decades. The possibility to target the drug to the diseased site, by avoiding side effects and lowering the required doses, strongly impulses the development of this kind of technology. Magnetic nanotechnology presents the additional advantage related to nanosystems that may be easily guided by the aid of an external magnetic field. This property improves the targeting capability and increases their potential in biomedical applications such as target drug delivery or MRI diagnostic. Iron oxides based nanosystems are currently the favorites to achieve these kinds of issues due to multiple reasons, but mainly to their low toxicity and biocompatibility. However, surface modification is often required to gain in stability, improve their physicochemical properties or even to raise the reactivity by means of functional groups incorporation. Silica appears as a highly attractive material to assess this objective.

In the Introductory section the general aspects of nanotechnology and nanomedicine are highlighted. Principles of iron oxides nanoparticles and their silica coat are described.

Nano-size in combination with magnetic properties gave rise to novel nanomaterials with improved properties, especially with regard to biomedical applications. This chapter is devoted to show the strong relationship between the design of nanoparticles and the final properties able to define its efficiency to the desired applications.

According to the literature, several inorganic materials may be chosen to assess magnetic nanodevices, however the iron oxides, such as magnetite and maghemite, are the preferred for several reasons. The property of superparamagnetism becomes crucial when the practical implementation of these nanosystems is intended in the biomedical field. This, and other properties strongly linked to the efficiency in biomedical applications are defined during the synthetic pathways. The most common preparative methods are here described highlighting the advantages and disadvantages as well as the properties of the obtained magnetic nanoparticles.

Coating of magnetic cores is strictly necessary to assess the interest and specific properties required for biomedical uses. In this regard, a classification of the most useful coatings is included highlighting the properties conferred by the selected coating material.

Characterization techniques able to evaluate the size, surface charge, functionality, and magnetism were also reported as a guide.

Silicon dioxide, SiO₂, is commonly known as silica. It may be found polymerized alone or in combination with other metals known as silicates.

This Chapter focuses on the biological, physiological, and biomedical issues related to silica. Although it was, in principle, considered as a highly toxic compound, this belief was reverted when several benign natural properties were discovered. In fact, silicon is actually considered as an essential trace element, being the most abundant in the body after iron and zinc. Therefore, several types of silica based materials are actually recognized as highly efficient in several biomedical applications. Among them bioglasses, star gels, mesoporous materials, and solid silica nanoparticles are found. The main applications range from drug delivery systems, target drug delivery, tissue regeneration, and diagnosis. All these applications already require a strict control over the properties of the designed silica materials.

Coating of magnetic nanoparticles is strongly required in order to obtain nanocarriers with suitable properties in terms of stability (low aggregation in aqueous media), surface functionality, and magnetism. Silica appears as an attractive compound to assess these goals. Among preventing aggregation, it is able to provide biocompatibility and the easy linkage of multiple ligands to specific applications.

Methodologies adopted to incorporate a silica layer on a magnetic core are varied; among them the Stöber method is the most widely employed. To a lesser extent, microemulsion, sodium silicate hydrolysis methods, sonochemical method among others are usually used for the synthesis.

From the above mentioned procedures it is feasible to prepare magnetic silica coated nanoparticles or even other kinds of magnetic silica materials. These features are achieved by simply modifying the experimental variables inherent to each method.

A comparison between these methodologies leads to the most adequate preparation technique as a function of the intended applications.

Biomedical applications of solid silica-coated magnetite nanoparticles are not highly reported in literature. Conventional biomedical uses are almost restricted to diagnostic issues. Other magnetic-silica materials such as mesoporous were last explored as target drug delivery.

Among the scarce literature reports, the existent are devoted to the use of solid silica coated magnetic nanoparticles as target drug delivery in the treatment of oncological diseases and in gene delivery and transfection. The use of these kinds of nanosystems as theranostics was also reported in the last few years. In this sense, the possibility is being explored to design a nanocarrier to be useful in more than one diagnostic technique, leading to multiple theranostics tools. In most cases, hard work on the design is required in order to assess selectivity and specificity in their function. To these ends silica coated magnetic nanoparticles are commonly modified with suitable ligands able to interact with biomarkers associated with the disease to treat.

The study of biodistribution and pharmacokinetics of nanosystems devoted to biomedical applications is mandatory, especially for nanodevices with potential applications as agents for targeted drug delivery. The physicochemical properties of silica coated magnetic nanoparticles such as composition, size, and surface charge play important roles in the biological impact of the nanosystems. The biodistribution pattern of the nanoparticles gives information about those organs which are feasible for target and also provides information to develop new strategies to improve targeting. Pharmacokinetics and metabolism are two important issues in terms of the behavior of the magnetic nanoparticles in the organism to ensure a good combination between nanoparticles and specific drugs to treat the desired pathologies.

This chapter reviews the biodistribution, pharmacokinetics, and metabolism of silica, iron oxide nanoparticles, and silica-coated magnetic nanoparticles in order to understand the role of each component in the biological features proposed.

Many factors govern the toxicological feature of silica-coated magnetic nanoparticles and they are associated with intrinsic features of the nanoparticles and also cell type. In vitro studies on cells and in vivo experiments trend to reveal the biocompatibility of silica and magnetite in the nano-scale.

The knowledge about toxicology of magnetic silica nanoparticles is intended not only to ensure safety of new devices intended for biomedical purposes such as drug targeting and delivery, but also as a tool for therapeutic insights if nanoparticles are present in selective toxicity. Thus, it is important to evaluate toxicological features associated with each novel nanodevice. This chapter describes the mechanisms associated with the toxicology of nano-silica, iron oxide magnetic nanoparticles, and the effects of the combination of the magnetic core with silica in different types of cells as well as the impact in vivo in different animals. All the aspects that govern toxicity are carefully considered and described to provide a global knowledge about the effect on the whole organism.

The lack of enough knowledge about the biological impact of silica-coated magnetic nanoparticles makes these systems non well-explored devices. However, the potential they have in terms of biomedical applications is really huge. Therefore, several applications in medicine are waiting to be explored and developed for silica-coated magnetic nanoparticles.