Physicochemical characteristics of silica nanoparticles tailored for nanomedicine

Silica nanoparticles have broad applications as multifunctional nanoparticle systems in nanomedicine. Silica nanoparticles possess a great potential as drug delivery systems: their small size, unique surface properties and loading capacities make them attractive for targeted drug delivery. Moreover, they can serve simultaneously as diagnostic tools. The attractive combination of drug delivery and simultaneous tracking of nanoparticles is known under the term “theranostic”. Hereby, diagnostic and therapeutic features can be united in the same particle with the controlled synthesis of silica nanoparticles. The drug delivery, stimuli responding abilities, and detectability with different imaging modalities can be incorporated into the same silica nanoparticle particle system. For successful use of nanoparticles in nanomedicine, their physicochemical characteristics need to be well-controlled to predict their behavior in biological matrices.
The size, shape, and surface characteristics of silica nanoparticles define their behavior at the nano-bio interface. In this study, silica nanoparticles were prepared with diverse size, shape, surface, and composition with the focus of having multifunctional silica nanoparticles and facilitating their use in biomedical applications.
For biomedical applications, the dispersion stability of nanoparticles is an important aspect for both diagnosis and therapy applications. In this study, dispersion stability of silica nanoparticles was evaluated by altering the surface characteristics. This was mainly achieved by physical adsorption of different copolymer compositions. Then, the emphasis was put on evaluating colloidal stability and residpersibility of particles in the biological relevant medium. Differences in re-dispersibility and dispersion stability of particles were observed by careful tuning of copolymer composition on the particle surfaces in biologically relevant media. Furthermore, physiological responses (i.e protein corona formation) to surface modified silica nanoparticles was investigated.
Before exerting an intracellular therapeutic effect, the silica nanoparticles need to be internalized by a specific target cell. Enhancement of cellular internalization can be provided by altering the size, shape and surface properties of the particles. The effect of shape and surface modification on the extent of cellular internalization was determined by preparing similarly sized and differently shaped particles with various surface charges. The obtained results revealed that the particle shape–induced uptake play a predominant role as compared to surface charge dependent uptake. We could show that particles with a higher aspect ratio of were internalized more quickly than their spherical counterparts. The surface charge of the particles remained as a secondary regulator to control the internalization of particles.
In therapeutic applications, targeted drug delivery is a promising approach which benefits from lower doses and avoiding side effects, because the drug is a) protected in a cargo and cannot freely diffuse and b) the targeting moiety leads to lesser side effects, as mainly cells express affinity that will lead to taking up of the nanoparticles. In this thesis, mesoporous silica nanoparticles were designed as drug carrier with active cellular targeting capability. Additionally, the particles were loaded with potential anticancer compound. The effect of the free potential anticancer compound and the silica nanoparticles incorporated compound was tested in vitro. The apoptotic effect of the potential anticancer compound was significantly enhanced compared to free compound with the employed targeted mesoporous silica nanoparticle based drug carrier.
Tracking of silica nanoparticles in the biological environment via different imaging modalities during the delivery of drug is an important feature for multifunctioning nanoparticles. This is usually achieved by the incorporation of an imaging probe into the silica network. The detectability of particles can be altered with the morphology of silica nanoparticles and the incorporation strategy of imaging probe into silica network. Furthermore, surface coating of the nanoparticles, leaching of the probe from the silica matrix, and the surrounding conditions can affect the detectability significantly. In the present thesis, these facts were evaluated in order to clarify their influences on detectability of particles via fluorescent and magnetic resonance imaging methodologies.
This thesis provides an overview addressing critical steps in the synthesis of silica nanoparticles based theranostic. Various methods were explored to obtain tailor-made silica nanoparticles for biomedical applications. The work provides deep insight into how the physicochemical properties influence their behavior in biological environment and can serve as a guideline to design safe and efficient theranostic systems.