Maslanka Figueroa, Sara and Fleischmann, Daniel and Beck, Sebastian and Goepferich, Achim (2020) The Effect of Ligand Mobility on the Cellular Interaction of Multivalent Nanoparticles. MACROMOLECULAR BIOSCIENCE, 20 (4): 1900427. ISSN 1616-5187, 1616-5195
Full text not available from this repository. (Request a copy)Abstract
Multivalent nanoparticle binding to cells can be of picomolar avidity making such interactions almost as intense as those seen with antibodies. However, reducing nanoparticle design exclusively to avidity optimization by the choice of ligand and its surface density does not sufficiently account for controlling and understanding cell-particle interactions. Cell uptake, for example, is of paramount significance for a plethora of biomedical applications and does not exclusively depend on the intensity of multivalency. In this study, it is shown that the mobility of ligands tethered to particle surfaces has a substantial impact on particle fate upon binding. Nanoparticles carrying angiotensin-II tethered to highly mobile 5 kDa long poly(ethylene glycol) (PEG) chains separated by ligand-free 2 kDa short PEG chains show a superior accumulation in angiotensin-II receptor type 1 positive cells. In contrast, when ligand mobility is constrained by densely packing the nanoparticle surface with 5 kDa PEG chains only, cell uptake decreases by 50%. Remarkably, irrespective of ligand mobility and density both particle types have similar EC50 values in the 1-3 x 10(-9) m range. These findings demonstrate that ligand mobility on the nanoparticle corona is an indispensable attribute to be considered in particle design to achieve optimal cell uptake via multivalent interactions.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PEG CHAIN-LENGTH; POLYETHYLENE-GLYCOL; CONVERTING-ENZYME; RECEPTOR DENSITY; MOLECULAR-WEIGHT; LINKER LENGTH; II RECEPTOR; IN-VITRO; DELIVERY; SIZE; cellular interactions; ligand density; ligand mobility; multivalency; polymer nanoparticles |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Technology (Prof. Göpferich) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Mar 2021 09:57 |
| Last Modified: | 30 Mar 2021 09:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45089 |
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