Encapsulation of manganese dioxide nanoparticles into layer-by-layer polymer capsules for the fabrication of antioxidant microreactors

Abstract

Oxidative stress is caused by the accumulation of reactive oxygen and nitrogen species (ROS and RNS) in the cellular microenvironment. These ROS and RNS damage important cell structures leading to cell apoptosis and senescence, thus causing a detrimental effect on numerous disease pathologies such as osteoarthritis, neurodegeneration and cardiovascular diseases. For this reason, there is a growing interest in the development of antioxidant biomaterials that can eventually regulate the levels of ROS/RNS and prevent oxidative stress. The encapsulation of antioxidant enzymes (e.g., catalase or superoxide dismutase) on polymer microcapsules fabricated via the layer-by-layer (LbL) approach represents a promising strategy within this context. The diffusion of reagents and by-products through the shell of these microcapsules is timely and spatially controlled, allowing the bio-chemical reaction between ROS/RNS and the encapsulated enzyme. However, natural enzymes usually present low stability, high cost and difficult storage, which could limit their potential application in the biomedical field. Hence, nanomaterials with intrinsic enzyme-like characteristics (i.e., nanozymes) have been considered as inorganic alternatives. In the present work, manganese dioxide nanoparticles were encapsulated into LbL polymer microcapsules to yield synthetic antioxidant microreactors. These microreactors efficiently scavenged hydrogen peroxide (H2O2) from solution and protected cells from oxidative stress in an in vitro model. The versatility of the synthetic procedure presented herein allows the fabrication of capsules with either positive or negative surface charge, which has a direct impact on the cytotoxicity and cell interaction. This study represents accordingly a novel strategy to obtain antioxidant polymer microreactors based on synthetic (nano)materials for the treatment of oxidative stress.