Physicochemical characteristics of silicananoparticles tailored for nanomedicine
Başlık çevirisi mevcut değil.
- Tez No: 402921
- Danışmanlar: PROF. JESSICA M. ROSENHOLM
- Tez Türü: Doktora
- Konular: Mühendislik Bilimleri, Engineering Sciences
- Anahtar Kelimeler: Belirtilmemiş.
- Yıl: 2016
- Dil: İngilizce
- Üniversite: Åbo Akademi University
- Enstitü: Yurtdışı Enstitü
- Ana Bilim Dalı: Belirtilmemiş.
- Bilim Dalı: Belirtilmemiş.
- Sayfa Sayısı: 127
Özet
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Özet (Çeviri)
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 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“theranostics”. Hereby, diagnostic and therapeutic features can be united in the same partide with the controlled synthesis of silica nanoparticles. 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 endowing the nanoparticles with multifunctionality and facilitating their use in biomedical applications. The dispersion stability of nanoparticles is an important aspect for both diagnosis and therapy applications. In this study, the dispersion stability of silica nanoparticles was evaluated after altering the surface physicochemical characteristics by a surface coating process. The process was mainly achieved by physical adsorption of copolymers composed of polyethylene glycol grafted polyethyleneimine (PEG-PEI) prepared with two different grafting ratios. Then, the emphasis was put on evaluating the colloidal stability and redispersibility of particles in the biologically relevant medium. Differences in redispersibility and dispersion stability of particles were observed by tuning of PEG-PEI composition on the partide surfaces. Furthermore, physiological responses (i.e. protein corona formation) to surface modified silica nanoparticles were investigated. In therapeutic applications, when the nanoparticles are designed as drug carriers, internalization of particles by target cells is aimed in order to exert intracellular therapeutic effects. Enhancement in the cellular internalization of nanoparticles can be facilitated by altering the size, shape and surface properties of the particles. In this thesis, silica nanoparticles with spherical and rod-like shapes, porous, non-porous and hollow structures were prepared on the submicron scale for biomedical purposes. Among these approaches, the extent of nanoparticle internalization was altered by modifying the shape and surface modification by preparing similarly sized spherical and rod-like particles with various net surface charges. The obtained results revealed that the partide shape-induced uptake play a predominant role as compared to surface charge dependent uptake. We could show that particles with a higher aspect ratio were internalized more than their spherical counterparts. The surface charge of the particles remained a secondary regülatör 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 to healthy cells. By the targeted drug deliver strategy, drugs can be protected in a drug delivery system (DDS), e.q. particulate drug delivery system and cannot freely diffuse, and the uptake of the DDS via specific ligand-receptor interaction, where the targeted receptors are mainly expressed at lesion sites, can be provided. Therefore, specific uptake of the DDS mainly by the injured cells reduces the side effects. In this thesis, mesoporous silica nanoparticles were designed as drug carrier with active cellular targeting capability. Additionally, the particles were loaded with a potential anticancer compound. The effect of the free potential anticancer compound and the silica nanoparticle 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 DDS. Tracking of silica nanoparticles in the biological environment via different imaging modalities during the delivery of drug is an important feature for multifunctional nanoparticles. This is usually achieved by the incorporation of an imaging probe into the silica network. The detectability of particles can be altered by the structural and morphology of silica nanoparticles, as well as 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 pH can affect the detectability significantly. In the present thesis, these phenomena were evaluated in order to clarify their influence on detectability of particles via fluorescent and magnetic resonance imaging methodologies. The thesis addresses the critical steps in the synthesis of silica nanoparticles to be used in theranostic applications. Various methods were explored to obtain tailor-made silica nanoparticles. The work provides deep insight into how the physicochemical properties of silica nanoparticles influence their fate in biological environment and can serve as a guideline to design safe and efficient theranostic systems.
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