Abstract
Antibody-modified drug delivery systems in the nano-range have the ability to overcome current challenges for treating diseases due to their high specificity towards the targeted body region. However, no antibody-bound nanocarrier has been clinically approved to date. This missing clinical approval may be a result of the conjugation strategy that influences the spatial orientation of the attached antibody on the nanocarriers' surface. What is not missing, however, is a diverse selection of antibody to nanocarrier conjugation strategies that determine the success of an antibody functionalized drug delivery system. In this paper, two antibody conjugation strategies were compared by conjugating the surface of cross-linked starch iron oxide nanocarriers with specifically modified CD11c monoclonal antibodies. The antibody nanocarrier conjugates, synthesized either by the chemistry of thiol-maleimide coupling or copper-free click chemistry, were analyzed by flow cytometry to determine their binding affinity towards a murine dendritic cell line (DC2.4). In the cell uptake, different antibody amounts on the nanocarrier could induce a dendritic cell uptake for both conjugation strategies. However, blocking experiments further highlighted the importance of the orientation of the antibody on to the nanocarriers' surface. While the antibodies which were attached via the copper-free click chemistry were oriented, maleimide synthesized conjugates presented their antibodies randomly on the surface. Lastly, to evaluate the in vivo properties of the antibody modified nanocarriers, targeting experiments with mouse plasma were performed, and it was proven that the biomolecular corona does not diminish the targeting efficiency.
Highlights
Antibody-modified drug delivery systems in the nano-range have the ability to overcome current challenges for treating diseases due to their high specificity towards the targeted body region
The targeting efficiency of the resulting nanocarrier conjugates was analyzed in a cell-based assay via flow cytometry and confocal laser scanning microscopy
It was demonstrated that copper-free click chemistry generated nanocarrier conjugates surpass the efficacy of thiol–maleimide chemistry produced conjugates
Summary
Antibody-modified drug delivery systems in the nano-range have the ability to overcome current challenges for treating diseases due to their high specificity towards the targeted body region. No antibody-bound nanocarrier has been clinically approved to date This missing clinical approval may be a result of the conjugation strategy that influences the spatial orientation of the attached antibody on the nanocarriers’ surface. Numerous strategies have been developed to attach antibodies to the surface of nanocarriers These strategies include the physical adsorption, covalent bonding, adapter molecules, or the combination of these concepts.[4] Despite the simplicity or straightforwardness of these conjugation concepts in theory, the implementation is challenging.[5] For instance, the Fab regions of the antibody should remain unaffected during the modification and immobilization process, because this region mediates the antigen recognition.[6]. Paper specific cytotoxic T-lymphocyte (CTL), which can eventually enable a tumor regression[7,8] In this process, dendritic cells, which are APCs, play a crucial role because they initiate and regulate these immune responses.[9]
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