Hyperbranched Polyglycerol‐Grafted Superparamagnetic Iron Oxide Nanoparticles: Synthesis, Characterization, Functionalization, Size Separation, Magnetic Properties, and Biological Applications

Abstract For biomedical application of nanoparticles, the surface chemical functionality is very important to impart additional functions, such as solubility and stability in a physiological environment, and targeting specificity as an imaging probe and a drug carrier. Although polyethylene glycol (PEG) has been used extensively, here, it is proposed that hyperbranched polyglycerol (PG) is a good or even better alternative to PEG. Superparamagnetic iron oxide nanoparticles (SPIONs) prepared using a polyol method are directly functionalized with PG through ring‐opening polymerization of glycidol. The resulting SPION‐PG is highly soluble in pure water (>40 mg mL⁻¹) and in a phosphate buffer solution (>25 mg mL⁻¹). Such high solubility enables separation of SPION‐PG according to size using size exclusion chromatography (SEC). The size‐separated SPION‐PG shows a gradual increase in transverse relaxivity (r₂) with increasing particle size. For biological application, SPION‐PG is functionalized through multistep organic transformations (–OH → –OTs (tosylate) → –N₃ → –RGD) including click chemistry as a key step to impart targeting specificity by immobilization of cyclic RGD peptide (Arg‐Gly‐Asp‐D‐Tyr‐Lys) on the surface. The targeting effect is demonstrated by the cell experiments; SPION‐PG‐RGD is taken up by the cells overexpressing α_vβ₃‐integrin such as U87MG and A549.