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

Ruirui Qiao, Changkui Fu, Yuhuan Li, Xiaole Qi, Dalong Ni, Aparna Nandakumar, Ghizal Siddiqui, Haiyan Wang, Zheng Zhang, Tingting Wu, Jian Zhong, Shi-Yang Tang, Shuaijun Pan, Cheng Zhang, Michael R. Whittaker, Jonathan W. Engle, Darren J. Creek, Frank Caruso, Pu Chun Ke, Weibo CaiAndrew K. Whittaker, Thomas P. Davis

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54 Citations (Scopus)


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 have huge potential to be employed as an advantageous alternative to PEG for the surface functionalization of a variety of nanoparticles for long circulation and improved delivery.

Original languageEnglish
Article number2000406
Number of pages13
JournalAdvanced Science
Issue number13
Publication statusPublished - May 2020


  • long circulation
  • low-fouling
  • nanoparticles
  • sulfoxide-containing polymers

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