title: Preparation of highly dispersible and tumor-accumulative, iron oxide nanoparticles Multi-point anchoring of PEG-b-poly(4-vinylbenzylphosphonate) improves performance significantly.
abstract: This paper describes the preparation of iron oxide nanoparticles, surface of which was coated with extremely high immobilization stability and relatively higher density of poly(ethylene glycol) (PEG), which are referred to as PEG protected iron oxide nanoparticles (PEG-PIONs). The PEG-PIONs were obtained through alkali coprecipitation of iron salts in the presence of the PEG-poly(4-vinylbenzylphosphonate) block copolymer (PEG-b-PVBP). In this system, PEG-b-PVBP served as a surface coating that was bound to the iron oxide surface via multipoint anchoring of the phosphonate groups in the PVBP segment of PEG-b-PVBP. The binding of PEG-b-PVBP onto the iron oxide nanoparticle surface and the subsequent formation of a PEG brush layer were proved by FT-IR, zeta potential, and thermogravimetric measurements. The surface PEG-chain density of the PEG-PIONs varied depending on the [PEG-b-PVBP]/[iron salts] feed-weight ratio in the coprecipitation reaction. PEG-PIONs prepared at an optimal feed-weight ratio in this study showed a high surface PEG-chain surface density (≈0.8 chainsnm(-2)) and small hydrodynamic diameter (<50 nm). Furthermore, these PEG-PIONs could be dispersed in phosphate-buffered saline (PBS) that contains 10% serum without any change in their hydrodynamic diameters over a period of one week, indicating that PEG-PIONs would provide high dispersion stability under in vivo physiological conditions as well as excellent anti-biofouling properties. In fact we have confirmed the prolong blood circulation time and facilitate tumor accumulation (more than 15% IDg(-1) tumor) of PEG-PIONs without the aid of any target ligand in mouse tumor models. The majority of the PEG-PIONs accumulated in the tumor by 96 h after administration, whereas those in normal tissues were smoothly eliminated by 96 h, proving the enhancement of tumor selectivity in the PEG-PION localization. The results obtained here strongly suggest that originally synthesized PEG-b-PVBP, having multipoint anchoring character by the phosphonate groups, is rational design for improvement in nanoparticle as in vivo application. Two major points, viz., extremely stable anchoring character and dense PEG chains tethered on the nanoparticle surface, worked simultaneously to become PEG-PIONs as an ideal biomedical devices intact for prolonged periods in harsh biological environments.
authors: Department of Materials Science, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8573, Japan.
authors: Kodai
authors: K
authors: Ujiie
authors: Naoki
authors: N
authors: Kanayama
authors: Kei
authors: K
authors: Asai
authors: Mikio
authors: M
authors: Kishimoto
authors: Yusuke
authors: Y
authors: Ohara
authors: Yoshimasa
authors: Y
authors: Akashi
authors: Keiichi
authors: K
authors: Yamada
authors: Shinji
authors: S
authors: Hashimoto
authors: Tatsuya
authors: T
authors: Oda
authors: Nobuhiro
authors: N
authors: Ohkohchi
authors: Hideto
authors: H
authors: Yanagihara
authors: Eiji
authors: E
authors: Kita
authors: Masayuki
authors: M
authors: Yamaguchi
authors: Hirofumi
authors: H
authors: Fujii
authors: Yukio
authors: Y
authors: Nagasaki
mesh_terms: D005290:Ferric Compounds / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry*; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*
chemical_list: D005290:Ferric Compounds; D011108:Polymers; C000499:ferric oxide; D011092:Polyethylene Glycols