Proteins play a crucial role in life, taking part in all vital process in the body, and are therefore used as therapeutic agents in a diverse range of biomedical applications. When... Show more Proteins play a crucial role in life, taking part in all vital process in the body, and are therefore used as therapeutic agents in a diverse range of biomedical applications. When administrated into bodily fluids, most native proteins are prone to degradation or inactivation process. The challenges of protein delivery are overcoming poor stability, low permeability toward cell membrane. Among all existing materials for protein delivery, mesoporous silica nanoparticles (MSNs) are one of the most promising intracellular nanocarriers due to its key properties: biocompatible, straightforward synthesis, and surface modification. For various biomedical applications, monodisperse MSNs with a particle size in the 50-200 nm range,3 controllable surface chemistry,4 and a large pore size (> 5 nm) are desired. This thesis presents a new method to synthesize large disc-like pore (10 ± 1 nm) containing MSNs with an elongated cuboidal-like geometry (90 × 43 nm), which effectively encapsulate and release proteins. Show less
In this thesis the thermal- and photo-substitution behavior of polypyridyl ruthenium complexes is described at the surface of lipid bilayers and in homogeneous solutions. It is shown that the... Show moreIn this thesis the thermal- and photo-substitution behavior of polypyridyl ruthenium complexes is described at the surface of lipid bilayers and in homogeneous solutions. It is shown that the successive thermal binding and light-induced unbinding of the cationic ruthenium complex at the surface of the lipid bilayer requires negatively charged liposomes and ruthenium complexes containing moderately hindered N-N bidentate ligands. Our results in homogeneous solution show that changing the steric hindrance of the bidentate ligand influences both the photo- and thermal reactivities of these complexes, by altering the mechanism of the Ru-S bond formation. It is also shown that the Ru-S bond formation at the surface of negative lipid bilayers is faster than the same reaction in homogenous aqueous solutions, and a two-steps mechanism is proposed for the thermal coordination of ruthenium aqua complexes at membrane-embedded ligands. Furthermore, the application of ruthenium-functionalized liposomes in drug delivery is discussed. In vitro tests on cancer cell lines show that neutral liposomes functionalized with ruthenium compounds are more readily taken up by cancer cells than ruthenium-free liposomes. The liposome samples with ruthenium compounds are shown to be poorly cytotoxic in the dark. After light irradiation, the cytotoxicity increased at least up to five times for ruthenium complexes supported on non-PEGylated liposomes. Finally, the photoactivation of polypyridyl complexes with low-energy photons was studied using a photosensitization approach. A photosubstitution reaction was made faster upon yellow light irradiation than upon blue light irradiation by covalently linking a rhodamine B dye to the ruthenium complex. Show less