Zusammenfassung
One of the central impediments for the clinical translation of targeted nanomaterials is their extensive off-target deposition, which can be mainly attributed to the addressed cellular surface structures being ubiquitously present in various other regions, such as the vascular system. This is especially important for the integrin receptor family, which is frequently addressed with ligands such as ...
Zusammenfassung
One of the central impediments for the clinical translation of targeted nanomaterials is their extensive off-target deposition, which can be mainly attributed to the addressed cellular surface structures being ubiquitously present in various other regions, such as the vascular system. This is especially important for the integrin receptor family, which is frequently addressed with ligands such as cRGD (cyclic Arg-Gly-Asp-d-Phe-Lys). Aside from their upregulation during tumor progression, integrins also play a prominent physiological role in endothelial cells, to which particles are exposed immediately after injection. However, there is a lack of understanding of how to modulate the usually undesirable interaction of nanoparticles (NPs) with these cells, especially under physiological conditions, that include the imminent impact of blood flow dynamics on NP behavior. Therefore, in this study, we introduced a steric shielding concept that is based on the addition of longer poly(ethylene glycol) chains into the NP corona, thereby individually camouflaging the ligand activity of cRGD-functionalized polymer NPs. More so, we implemented a method of endothelial cell culture and particle incubation under a constant flow, mimicking physiological conditions (shear stress = 2–14 dyn cm–2). By controlling the surface density (25–75%) and length (3.5 vs 5 kDa) of respective shielding elements, in vitro NP uptake into model endothelial cells could be precisely steered. Additionally, the NP–cell interplay showed significant differences when examined under dynamic conditions, confirming the need for such investigations to improve the clinical translation of nanomaterials.
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