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Maslanka-Figueroa, Sara ; Fleischmann, Daniel ; Beck, Sebastian ; Goepferich, Achim

The Effect of Ligand Mobility on the Cellular Interaction of Multivalent Nanoparticles

Maslanka-Figueroa, Sara , Fleischmann, Daniel, Beck, Sebastian und Goepferich, Achim (2020) The Effect of Ligand Mobility on the Cellular Interaction of Multivalent Nanoparticles. Macromolecular Bioscience 20, S. 900427.

Veröffentlichungsdatum dieses Volltextes: 26 Feb 2020 08:50
Artikel
DOI zum Zitieren dieses Dokuments: 10.5283/epub.41678


Zusammenfassung

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 ...

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.



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Details

DokumentenartArtikel
Titel eines Journals oder einer ZeitschriftMacromolecular Bioscience
Verlag:Wiley
Ort der Veröffentlichung:WEINHEIM
Band:20
Seitenbereich:S. 900427
Datum2020
InstitutionenChemie und Pharmazie > Institut für Pharmazie > Lehrstuhl Pharmazeutische Technologie (Prof. Göpferich)
Identifikationsnummer
WertTyp
10.1002/mabi.201900427DOI
Stichwörter / KeywordsPEG 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
Dewey-Dezimal-Klassifikation600 Technik, Medizin, angewandte Wissenschaften > 615 Pharmazie
StatusVeröffentlicht
BegutachtetJa, diese Version wurde begutachtet
An der Universität Regensburg entstandenJa
URN der UB Regensburgurn:nbn:de:bvb:355-epub-416783
Dokumenten-ID41678

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