5.1 18 F-RADIOLABELING OF SURFACE-MODIFIED PSi
7 SUMMARY AND CONCLUDING REMARKS
In summary, radiolabeling with 18F has been established as a robust tool to investigate PSi micro- and nanoparticle behavior in vivo. We have shown that direct nucleophilic substitution of 18F– to various surface-modified PSi is feasible within the limits set by the 109.8-minute half-life of the isotope.
Depending of the surface chemistry, the substitution reaction was shown to occur either to a Si–H, Si–O–Si, or Si–F groups on the PSi surface. The synthesized Si–18F bond was remarkably stable in physiological conditions both in vitro and in vivo, highlighting one of the undisputable strengths of the selected radiolabeling strategy. Furthermore, the surface chemistry and other properties of the nanoparticles were not changed by the conditions of the radiolabeling reaction confirming that they could be used as tracers for non-radiolabeled PSi. [18F]THCPSi nanoparticles were shown to exhibit high biocompatibility in vitro, prompting their use in the animal studies. Post
radiosynthetic biofunctionalization of [18F]THCPSi nanoparticles with a self-assembled layer of a fungal hydrophobin was successfully realized in order to develop a tracer for HFBII-THCPSi nanoparticles. Biodistribution studies with HFBII-[18F]THCPSi nanoparticles revealed mucoadhesive and gastro
retentive properties that encourage further studies with the HFBII-bio
functionalized nanoparticles as drug delivery carriers in the oral route. In addition, the HFBII coating markedly altered the plasma protein adsorption to THCPSi nanoparticles and consequently their biodistribution after intra
venous administration, illustrating the importance of the knowledge of unmodified drug delivery carrier biodistribution to the development of tailored carriers for intravenous delivery.
In conclusion, the studies presented in this work contribute new methodo
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