Calcium phosphate nanoparticle surface modification by click chemistry and applications in biomedicine
With this thesis a new approach for the surface modification of calcium phosphate nanoparticles (CaP NPs) was developed and applications in biomedicine were evaluated. The concept of click chemistry, specifically the copper catalysed click reaction (CuAAC) and strain-promoted azide-alkyne cycloaddition (SPAAC), was used to modify the nanoparticle surface. These methods guarantee a durable interaction due to the covalent bond formation. The reaction was evaluated using different dye molecules and highly fluorescent nanoparticles were obtained. These nanoparticles were suitable and studied by super-resolution fluorescence microscopy methods such as Structured Illumination Microscopy (SIM) and Stochastic Optical Reconstruction Microscopy (STORM). In general, the azide-terminated calcium phosphate nanoparticles can be reacted with other alkyne-carrying molecules. For example, an alkyne-derivate HIV-1 envelope glycoprotein was attached to the calcium phosphate nanoparticle, and compared to a non-specific coupling method using sulfo-SMCC crosslinker. Furthermore, calcium phosphate nanoparticles with an additional internal loading (e.g. pHBsAg and siRNA-TNF-alpha) were also prepared and studied in vitro and in vivo for potential applications for vaccination or as a direct application of the nanomaterial within the biomedicine. As demonstrated in this thesis, the scope of calcium phosphate nanoparticles is very broad, and combined with an appropriate chemical surface modification method, like CuAAC and SPAAC, the application of CaP NPs can be extended. Thus, with an internal protected loading and an external chemically modified surface, the calcium phosphate nanoparticle system continues to be a highly versatile particle within the 50-100 nm range for biomedicine applications
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