A dual-component carrier with both non-enzymatic and enzymatic antioxidant activity towards ROS depletion

Biomater Sci. 2019 Nov 1;7(11):4813-4826. doi: 10.1039/c9bm00913b. Epub 2019 Sep 19.

Abstract

While ROS display crucial functions in many physiological processes, elevated ROS levels are also related to the initiation and progression of many severe diseases such as cancer, cardiovascular conditions or neurologic disorders. Research approaches to diminish ROS levels during disease progression are currently being focused on the therapeutic administration of antioxidant enzymes. However, enzyme administration suffers from several limitations including their fast elimination from blood upon administration, thus making crucial the development of enzyme encapsulating platforms. We have recently reported a multicompartment architecture constituted by two inherently different types of materials, i.e., polymeric microgels and liposomes. Poly(N-isopropylacrylamide-co-acrylic acid) microgels decorated with liposomes and subsequently coated by a protective poly(dopamine) shell (PDA) combine the benefits of both systems while minimizing some of their drawbacks. Herein, we exploit this dual-component platform as a microreactor for ROS depletion. We combine the intrinsic PDA's antioxidant properties with the encapsulation of the catalase enzyme within the liposomal compartments. The surface of the carrier is further functionalised with a poly(ethylene glycol) layer and the low fouling properties are demonstrated in terms of reduction of protein adsorption and cellular uptake. The potential of the carrier as an antioxidant microreactor is shown by its ability to deplete superoxide radicals and hydrogen peroxide, which can also take place in the presence of the two relevant cell lines.

MeSH terms

  • Acrylamides / chemistry
  • Acrylamides / metabolism*
  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Antioxidants / metabolism*
  • Catalase / chemistry
  • Catalase / metabolism*
  • Cells, Cultured
  • Indoles / chemistry
  • Indoles / metabolism*
  • Liposomes / chemistry
  • Liposomes / metabolism
  • Mice
  • Particle Size
  • Polymers / chemistry
  • Polymers / metabolism*
  • RAW 264.7 Cells
  • Reactive Oxygen Species / metabolism*
  • Surface Properties

Substances

  • Acrylamides
  • Antioxidants
  • Indoles
  • Liposomes
  • N-isopropylacrylamide-acrylic acid copolymer
  • Polymers
  • Reactive Oxygen Species
  • polydopamine
  • Catalase