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

• Published in: Advanced science 2020-07, Vol.7 (13), p.2000406-n/a
• Main Authors: Qiao, Ruirui, Fu, Changkui, Li, Yuhuan, Qi, Xiaole, Ni, Dalong, Nandakumar, Aparna, Siddiqui, Ghizal, Wang, Haiyan, Zhang, Zheng, Wu, Tingting, Zhong, Jian, Tang, Shi‐Yang, Pan, Shuaijun, Zhang, Cheng, Whittaker, Michael R., Engle, Jonathan W., Creek, Darren J., Caruso, Frank, Ke, Pu Chun, Cai, Weibo, Whittaker, Andrew K., Davis, Thomas P.
• Format: Article
• Language: English
• Subjects: Bisphosphonates; Contrast agents; Cytokines; Cytotoxicity; Efficiency; Immune system; Ligands; long circulation; low‐fouling; Magnetic resonance imaging; Nanoparticles; Polyethylene glycol; Polymerization; Polymers; Protective coatings; Proteins; sulfoxide‐containing polymers
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202000406

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. An innovative class of sulfoxide‐containing polymer is used as an exceptional surface functionalization material for nanoparticles. The highly hydrophilic nature of the polymer endows nanoparticles with remarkable low‐fouling property as demonstrated by weak interaction with plasma proteins, prolonged blood circulation, and improved biodistribution profile of conjugated nanoparticles.