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Architectural Modification of Conformal PEG‐Bottlebrush Coatings Minimizes Anti‐PEG Antigenicity While Preserving Stealth Properties
Author(s) -
Joh Daniel Y.,
Zimmers Zackary,
Avlani Manav,
Heggestad Jacob T.,
Aydin Hakan B.,
Ganson Nancy,
Kumar Shourya,
Fontes Cassio M.,
Achar Rohan K.,
Hershfield Michael S.,
Hucknall Angus M.,
Chilkoti Ashutosh
Publication year - 2019
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201801177
Subject(s) - antigenicity , ethylene glycol , peg ratio , polymer brush , methacrylate , bovine serum albumin , polymer , materials science , surface modification , polymer chemistry , polyethylene glycol , copolymer , chemistry , combinatorial chemistry , chromatography , biochemistry , polymerization , organic chemistry , antigen , biology , composite material , finance , economics , genetics
Poly(ethylene glycol) (PEG), a linear polymer known for its “stealth” properties, is commonly used to passivate the surface of biomedical implants and devices, and it is conjugated to biologic drugs to improve their pharmacokinetics. However, its antigenicity is a growing concern. Here, the antigenicity of PEG is investigated when assembled in a poly(oligoethylene glycol) methacrylate (POEGMA) “bottlebrush” configuration on a planar surface. Using ethylene glycol (EG) repeat lengths of the POEGMA sidechains as a tunable parameter for optimization, POEGMA brushes with sidechain lengths of two and three EG repeats are identified as the optimal polymer architecture to minimize binding of anti‐PEG antibodies (APAs), while retaining resistance to nonspecific binding by bovine serum albumin and cultured cells. Binding of backbone‐ versus endgroup‐selective APAs to POEGMA brushes is further investigated, and finally the antigenicity of POEGMA coatings is assessed against APA‐positive clinical plasma samples. These results are applied toward fabricating immunoassays on POEGMA surfaces with minimal reactivity toward APAs while retaining a low limit‐of‐detection for the analyte. Taken together, these results offer useful design concepts to reduce the antigenicity of polymer brush‐based surface coatings used in applications involving human or animal matrices.