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Phosphonylation Controls the Protein Corona of Multifunctional Polyglycerol‐Modified Nanocarriers
Author(s) -
Danner AnnKathrin,
Schöttler Susanne,
Alexandrino Evandro,
Hammer Sophie,
Landfester Katharina,
Mailänder Volker,
Morsbach Svenja,
Frey Holger,
Wurm Frederik R.
Publication year - 2019
Publication title -
macromolecular bioscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 105
eISSN - 1616-5195
pISSN - 1616-5187
DOI - 10.1002/mabi.201800468
Subject(s) - nanocarriers , chemistry , protein adsorption , miniemulsion , ethylene glycol , peg ratio , phosphonate , polymer , drug delivery , biophysics , chemical engineering , nanotechnology , materials science , organic chemistry , monomer , finance , engineering , economics , biology
Abstract Nanocarriers are a platform for modern drug delivery. In contact with blood, proteins adsorb to nanocarriers, altering their behavior in vivo. To reduce unspecific protein adsorption and unspecific cellular uptake, nanocarriers are modified with hydrophilic polymers like poly(ethylene glycol) (PEG). However, with PEG the attachment of further functional structures such as targeting units is limited. A method to introduce multifunctionality via polyglycerol (PG) while maintaining the hydrophilicity of PEG is introduced. Different amounts of negatively charged phosphonate groups (up to 29 mol%) are attached to the multifunctional PGs ( M n 2–4 kg mol −1 , Ð < 1.36) by post‐modification. PGs are used in the miniemulsion/solvent evaporation procedure to prepare model nanocarriers. Their behavior in human blood plasma is investigated to determine the influence of the negative charges on the protein adsorption. The protein corona of PGylated nanocarriers is similar to PEGylated analogs (on same nanocarriers), but the protein pattern could be gradually altered by the integration of phosphonates. This is the first report on the gradual increase of negative charges on nanocarriers and intriguingly up to a certain amount of phosphonate groups per nanocarrier the protein pattern remains relatively unchanged, which is important for the future design of nanocarriers.