Sulfoxide-Containing Polymer-Coated Nanoparticles Demonstrate Minimal Protein Fouling and Improved Blood Circulation

Advanced Science
Ruirui QiaoThomas P Davis

Abstract

Minimizing the interaction of nanomedicines with the mononuclear phagocytic system (MPS) is a critical challenge for their clinical translation. Conjugating polyethylene glycol (PEG) to nanomedicines is regarded as an effective approach to reducing the sequestration of nanomedicines by the MPS. However, recent concerns about the immunogenicity of PEG highlight the demand of alternative low-fouling polymers as innovative coating materials for nanoparticles. Herein, a highly hydrophilic sulfoxide-containing polymer-poly(2-(methylsulfinyl)ethyl acrylate) (PMSEA)-is used for the surface coating of iron oxide nanoparticles (IONPs). It is found that the PMSEA polymer coated IONPs have a more hydrophilic surface than their PEGylated counterparts, and demonstrate remarkably reduced macrophage cellular uptake and much less association with human plasma proteins. In vivo study of biodistribution and pharmacokinetics further reveals a much-extended blood circulation (≈2.5 times longer in terms of elimination half-life t1/2) and reduced accumulation (approximately two times less) in the organs such as the liver and spleen for IONPs coated by PMSEA than those by PEG. It is envisaged that the highly hydrophilic sulfoxide-containing polymers ...Continue Reading

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Methods Mentioned

BETA
size exclusion chromatography
PMSEA
dynamic light scattering
blood collection
density gradient centrifugation
PMA
X‐ray

Software Mentioned

STRINGdb
MaxQuant
Metaboanalyst
Excel
Inveon Research Workplace [ IRW
GraphPad Prism
Harmony High Content Imaging and Analysis
Cytoscape

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