Surveying for Surfaces that Resist the Adsorption of Proteins

Chapman, Robert; Ostuni, Emanuele; Takayama, Shuichi; Holmlin, R. Erik; Yan, Lin; Whitesides, George M.

doi:10.1021/ja000774f

Cited by 552 publications

(560 citation statements)

References 19 publications

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“…PEG had been widely used as a coating to generate biocompatible surfaces that are nonimmungenic, nonantigenic, and resist protein adsorption (Alcantar et al, 2000;Kingshott and Griesser, 1999;Malmsten and Van Alstine, 1996). The molecular basis of the protein repellant properties of PEG is reportedly attributed to a number of different interactions: steric repulsion due to the polymer chain, repulsion due to the presence of a hydration shell around the polymer chain, and/or electrostatic repulsion stemming from the polar monomeric units (Chapman et al, 2000;Harris and Zalipsky, 1997;Lee and Schaffer, 2003). For protein PEGylation, various types of crosslinking chemistry have been evaluated (Emoto et al, 1996;Kingshott et al, 2002;Roberts et al, 2002;Veronese, 2001;Veronese and Harris, 2002).…”

Section: Discussionmentioning

confidence: 99%

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

Lee

Maheshri

Kaspar³

et al. 2005

Biotechnol. Bioeng.

129

114

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AAV gene therapy vectors have significant clinical promise, but serum neutralization poses a challenge that must be overcome. We have examined the potential of conjugating the AAV surface with activated polyethylene glycol chains to protect the vector from neutralizing antibodies. Two key parameters were investigated: the polymer chain size and the PEG:lysine conjugation ratio. Transduction data revealed that the vector is fully infectious until a critical PEG conjugation reaction ratio was exceeded, and this critical level was found to vary with polymer chain size. At this key conjugation ratio, however, particles were moderately protected from serum neutralization, 2.3-fold over unmodified vector, demonstrating that there is a small window of PEGylation for which particles are still fully infective and benefit from antibody protection. TEM results and structural analysis indicate that the drop of infectivity as the PEG concentration is increased beyond the critical conjugation ratio may be due to a combination of steric interference with viral regions necessary for infection as well as reaction at important lysine residues. However, this first study analyzing the potential of PEG to protect AAV from serum neutralization shows that the approach has promise, which can be further enhanced if the locations of PEG attachment can be more finely controlled. ß

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Section: Discussionmentioning

confidence: 99%

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

Lee

Maheshri

Kaspar³

et al. 2005

Biotechnol. Bioeng.

129

114

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“…It has also been suggested that charge-neutrality is an essential feature of protein-resistant selfassembled monolayers (SAMs) (Chapman et al 2000, Ostuni et al 2001). However, most surfaces, including also nominally neutral materials, become charged to some extent upon immersion in water due to preferential adsorption of ions, ionization, or asymmetric dissociation.…”

Section: Introductionmentioning

confidence: 99%

Charged hydrophilic polymer brushes and their relevance for understanding marine biofouling

et al. 2016

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“…8,16 Observed exceptions to this general rule, such as formation of bioinert layers from zwitterionic 10,11 and hydroxyl-terminated oligomers, 8,24 however, indicate that this field of surface engineering is largely unexplored.…”

Section: Introductionmentioning

confidence: 99%

Surface-Bound Proteins with Preserved Functionality

et al. 2009

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Abstract-Biocompatibility of materials strongly depends on their surface properties. Therefore, surface derivatization in a controllable manner provides means for achieving interfaces essential for a broad range of chemical, biological, and medical applications. Bioactive interfaces, while manifesting the activity for which they are designed, should suppress all nonspecific interaction between the supporting substrates and the surrounding media. This article describes a procedure for chemical derivatization of glass and silicon surfaces with polyethylene glycol (PEG) layers covalently functionalized with proteins. While the proteins introduce the functionality to the surfaces, the PEGs provide resistance against nonspecific interactions. For formation of aldehyde-functionalized surfaces, we coated the substrates with acetals (i.e., protected aldehydes). To avoid deterioration of the surfaces, we did not use strong mineral acids for the deprotection of the aldehydes. Instead, we used a relatively weak Lewis acid for conversion of the acetals into aldehydes. Introduction of a,x-bifunctional polymers into the PEG layers, bound to the aldehydes, allowed us to covalently attach green fluorescent protein and bovine carbonic anhydrase to the surfaces. Spectroscopic studies indicated that the surface-bound proteins preserve their functionalities. The surface concentrations of the proteins, however, did not manifest linear proportionality to the molar fractions of the bifunctional PEGs used for the coatings. This finding suggests that surface-loading ratios cannot be directly predicted from the compositions of the solutions of competing reagents used for chemical derivatization.

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Surveying for Surfaces that Resist the Adsorption of Proteins

Cited by 552 publications

References 19 publications

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

Charged hydrophilic polymer brushes and their relevance for understanding marine biofouling

Surface-Bound Proteins with Preserved Functionality

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