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

Abstract

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 ( r 2 ) with increasing particle size. For biological application, SPION‐PG is functionalized through multistep organic transformations (–OH → –OTs (tosylate) → –N 3 → –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 v β 3 ‐integrin such as U87MG and A549.