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Development of stealth nanoparticles coated with poly(2-methoxyethyl vinyl ether) as an alternative to poly(ethylene glycol)
Authors:Kento Fujiura  Mitsuru Naito  Yukiko Tanaka  Masaru Tanaka  Yurie Nakanishi  Hirotaka Ejima  Lumi Negishi  Tomoya Kujirai  Hitoshi Kurumizaka  Seiichi Ohta  Kanjiro Miyata
Affiliation:1. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Maruzen Petrochemical Co., Ltd., Tokyo, Japan

Contribution: Conceptualization (lead), ?Investigation (lead), Methodology (lead), Visualization (lead), Writing - original draft (lead);2. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Contribution: Conceptualization (supporting), Project administration (supporting), Supervision (supporting), Writing - review & editing (supporting);3. Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka, Japan

Contribution: Methodology (supporting);4. Institute for Materials Chemistry and Engineering, Kyushu University, Fukuoka, Japan

Contribution: Funding acquisition (supporting), Methodology (supporting), Supervision (supporting), Writing - review & editing (supporting);5. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Contribution: Methodology (supporting);6. Institute for Quantitative Biosciences, The University of Tokyo, Tokyo, Japan

Contribution: Methodology (supporting);7. Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Contribution: Supervision (supporting);8. Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan

Abstract:Poly(ethylene glycol) (PEG) modification, also known as PEGylation, has been extensively used to improve the stability of nanoparticles for nanomedical applications. However, PEG exhibits antigenicity in some formulations, motivating researchers to explore alternative polymers. Herein, poly(vinyl ether) (PVE) derivatives are highlighted as promising alternatives to PEG because they form intermediate water molecules that suppress non-specific protein adsorption and platelet adhesion to the material surface. We prepared a water-soluble PVE derivative, poly(2-methoxyethyl vinyl ether) (PMOVE), and utilized it as a surface modifier for gold nanoparticles (AuNPs) as model nanoparticles. PMOVE with a thiol terminus was synthesized and confirmed to form an intermediate water molecule using differential scanning calorimetry. Similar to the synthesis of PEGylated AuNPs (PEG-AuNPs), PMOVE-modified AuNPs (PMOVE-AuNPs) were successfully fabricated with an appreciably high density of PMOVE palisades via a thiol-gold coordination reaction. Similar to PEG-AuNPs, PMOVE-AuNPs showed reduced serum protein adsorption and prolonged blood circulation. Additionally, no significant cytotoxicity was observed after incubation of a murine macrophage cell line, RAW264.7, with PMOVE-AuNPs. Our results indicate that the PMOVE modification increases the stealthiness of nanoparticles that is equivalent to that achieved by PEGylation.
Keywords:nanomedicine  PEGylation  poly(vinyl ether)  stealth polymer
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