Catechol-Bearing Polymeric Nanoparticles for Antioxidant Therapy
- PDF / 4,300,922 Bytes
- 6 Pages / 612 x 792 pts (letter) Page_size
- 65 Downloads / 337 Views
Catechol-Bearing Polymeric Nanoparticles for Antioxidant Therapy Urara Hasegawa1,2, Masaki Moriyama2, Hiroshi Uyama2, André J. van der Vlies2,3, Stéphanie Metzger4, Martin Ehrbar4 1
Frontier Research Base for Young Researchers, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 2 Department of Applied Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 3 Frontier Research Center, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka 565-0871, Japan. 4 Department of Obstetrics, University Hospital Zurich, Schmelzbergstrasse 12, 8091 Zürich, Switzerland.
ABSTRACT Polymeric nanoparticles having redox-active catechol moieties, a common structural motif found in naturally-occurring antioxidants, were developed. We synthesized an amphiphilic catechol-bearing polymer that self-assembled to form nanoparticles with a diameter of 126 nm. The nanoparticles showed enhanced ROS-scavenging activity compared to the small catecholic compound dopamine. Furthermore, the nanoparticles inhibited ROS-mediated angiogenesis as shown by the endothelial cell tube formation assay and the chicken chorioallantoic membrane (CAM) assay. INTRODUCTION Reactive oxygen species (ROS), such as hydrogen peroxide (H2O2), superoxide anion (O2•-), peroxyl radical (ROO•) and hydroxyl radical (OH•), are endogenously produced as a consequence of aerobic metabolism in the human body. [1, 2] Although the basal level of ROS is essential, overproduction of ROS induces tissue damage and inflammation, which is often associated with the initiation and progression of cancer and other oxidative stress-related diseases. [3, 4] Therefore, scavenging of ROS is of interest for treating these conditions. Antioxidant compounds have attracted attention due to their protective role against oxidative stress. Despite their promise in treatment of some diseases, these compounds show low bioavailability in vivo due to their poorly-controlled pharmacokinetics which limits their application. Recently, we reported block copolymer micelles having redox-active catechol moieties, a common structural motif found in naturally-occurring antioxidants. [5, 6] Amphiphilic block copolymers composed of poly(ethylene glycol) block and catechol-bearing block self-assembled in water to form micelles by hydrophobic interaction between catechol-bearing blocks. The micelles showed high stability against auto-oxidation under aerobic condition compared to the small catechol compound dopamine (DA). Furthermore, the micelles significantly inhibited ROS-mediated angiogenesis.
Since the catechol moieties were hydrophobic enough to drive micellization as shown by our previous work, we reasoned that randomly grafting of these groups to a hydrophilic polymer would induce self-assembly to form nanoparticles. Here, we prepared self-assembled nanoparticles (PDA-NPs) from poly(N-acryloyl glycine)-bearing catechol moieties (PDA). ROS scavenging activity of the PDA-NPs was evaluated by the
Data Loading...
