Development of stealth nanoparticles coated with poly(2‐methoxyethyl vinyl ether) as an alternative to poly(ethylene glycol)

Abstract

AbstractPoly(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.