Selective surface functionalization and cell uptake of reproducibly synthesized biocompatible nanocapsules
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Abstract
Recent developments in vaccine research demonstrate that engineered nanomaterials such as nanocarriers play an increasingly important role in modern medicine. The use of nanocarriers is an elaborate strategy that originally launched its involvement in cancer therapy. Next to the decrease of side-effects due to packaging of the drug, therapeutic efficacy is not limited to the sole delivery of the drug to its destination, but the carrier itself can also participate in the therapeutic approach using targeting moieties and smart materials.
Liposomal formulations are so far the most successful ones, representing the largest group of nanocarriers in clinical applications and trials, while other nanoparticulate materials have not shown a similar therapeutic scope yet. Reproducibility of nanocarrier syntheses is essential for successful translation to the clinic, however, this is difficult because nanoparticulate materials are, from a chemical point of view, extraordinarily complex. Furthermore, distinct physicochemical properties of the carriers are associated to biological characteristics, which are not fully understood yet.
This work aims to elucidate in detail the synthesis and surface functionalization of biocompatible nanocapsules, as potential drug delivery vehicles and the effects induced on a cellular level. In the first part it is shown that hydroxylethyl starch (HES) nanocapsules were reproducibly synthesized and biomolecules relevant for the targeting and selective proliferation of specific immune cells are attached to the surface, thus accomplishing the desired cell response. It is confirmed that also protein nanocapsules can be synthesized in the same manner and thermodynamic details for the binding constitutions are analyzed using a model system. In the third part it is shown that protein nanocapsules were synthesized using a bioorthogonal crosslinking approach, while revealing different uptake properties due to alteration of the surface constitution. In the fourth part, unambiguous localization of the protein nanocapsules inside cells is demonstrated, enabling elucidation of trafficking pathways.
In summary, an overall relationship of size, surface charge, and binding constitutions of different biocompatible nanocapsules, consisting of hydroxylethyl starch and proteins is given and their cellular uptake is illustrated. The findings are therefore an example for the analysis of structure-effect relationships for nanocarriers and are presenting further advances for nanocarrier characterizations and novel insights in order to improve clinical feasibility.