title: pH-Responsive biodegradable polymeric micelles with anchors to interface magnetic nanoparticles for MR imaging in detection of cerebral ischemic area.
abstract: A novel type of pH-responsive biodegradable copolymer was developed based on methyloxy-poly(ethylene glycol)-block-poly[dopamine-2-(dibutylamino) ethylamine-l-glutamate] (mPEG-b-P(DPA-DE)LG) and applied to act as an intelligent nanocarrier system for magnetic resonance imaging (MRI). The mPEG-b-P(DPA-DE)LG copolymer was synthesized by a typical ring opening polymerization of N-carboxyanhydrides (NCAs-ROP) using mPEG-NH2 as a macroinitiator, and two types of amine-terminated dopamine groups and pH-sensitive ligands were grafted onto a side chain by a sequential aminolysis reaction. This design greatly benefits from the addition of the dopamine groups to facilitate self-assembly, as these groups can act as high-affinity anchors for iron oxide nanoparticles, thereby increasing long-term stability at physiological pH. The mPEG moiety in the copolymers helped the nanoparticles to remain well-dispersed in an aqueous solution, and pH-responsive groups could control the release of hydrophobic Fe3O4 nanoparticles in an acidic environment. The particle size of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles was measured by dynamic light scattering (DLS) and cryo-TEM. The superparamagnetic properties of the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles were confirmed by a superconducting quantum interference device (SQUID). T2-weighted magnetic resonance imaging (MRI) of Fe3O4-loaded mPEG-b-P(DPA-DE)LG phantoms exhibited enhanced negative contrast with an r2 relaxivity of approximately 106.7 mM(-1) s(-1). To assess the ability of the Fe3O4-loaded mPEG-P(DE-DPA)LG micelles to act as MRI probes, we utilized a cerebral ischemia disease rat model with acidic tissue. We found that a gradual change in contrast in the cerebral ischemic area could be visualized by MRI after 1 h, and maximal signal loss was detected after 24 h post-injection. These results demonstrated that the Fe3O4-loaded mPEG-b-P(DPA-DE)LG micelles can act as pH-triggered MRI probes for diagnostic imaging of acidic pathological tissues.
authors.affiliation: Theranostic Macromolecules Research Center, School of Chemical Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea. dslee@skku.edu.
authors.forename: Hong Yu
authors.initials: HY
authors.lastname: Yang
authors.forename: Moon-Sun
authors.initials: MS
authors.lastname: Jang
authors.forename: Guang Hui
authors.initials: GH
authors.lastname: Gao
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Lee
authors.forename: Doo Sung
authors.initials: DS
authors.lastname: Lee
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D056945:Hep G2 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008823:Micelles; D011092:Polyethylene Glycols; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D058185:Magnetite Nanoparticles; D008823:Micelles; D011092:Polyethylene Glycols