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In this study, hybrid nanocubes composed of magnetite (Fe 3 O 4 ) and manganese dioxide (MnO 2 ), coated with U-251 MG cell-derived membranes (CM-NCubes) are synthesized. The CM-NCubes demonstrate a concentration-dependent oxygen generation (up to 15%), and, for the first time in the literature, an intracellular increase of temperature (6 °C) due to the exothermic scavenging reaction of hydrogen peroxide (H 2 O 2 ) is showed. Internalization studies demonstrate that the CM-NCubes are internalized much faster and at a higher extent by the homotypic U-251 MG cell line compared to other cerebral cell lines. The ability of the CM-NCubes to cross an in vitro model of the blood-brain barrier is also assessed. The CM-NCubes show the ability to respond to a static magnet and to accumulate in cells even under flowing conditions. Moreover, it is demonstrated that 500 µg mL -1 of sorafenib-loaded or unloaded CM-NCubes are able to induce cell death by apoptosis in U-251 MG spheroids that are used as a tumor model, after their exposure to an alternating magnetic field (AMF). Finally, it is shown that the combination of sorafenib and AMF induces a higher enzymatic activity of caspase 3 and caspase 9, probably due to an increment in reactive oxygen species by means of hyperthermia., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Excess reactive oxygen species (ROS) has been implicated in numerous diseases including cancer, cardiovascular and neurodegenerative diseases. Overexpression of ROS can lead to oxidative stress and subsequently to H 2 O 2 -mediated cell apoptosis. In this study, it was demonstrated that biodegradable PLGA microspheres coated with collagen type I and decorated with MnO 2 nanoparticles acted as ROS scavengers controlling the H 2 O 2 -mediated apoptosis of cells undergoing oxidative stress. The results showed that the functionalized collagen spheres can protect cells even under very harsh conditions of oxidative stress., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Reactive oxygen species (ROS) (H2 O2 , OCl(-) , (•) OH, O2 (-) ) are a family of reactive molecules that are generated intracellularly and are engaged in many biological processes. In physiological concentrations, ROS act as signaling molecules to a number of metabolic pathways; however, in excess they can be harmful to living organisms. Overproduction of ROS has been related to many pathophysiological conditions and a number of studies have been reported in elucidating their mechanism in these conditions. With the aim of harnessing this role, a number of imaging tools and therapeutic compounds have been developed. Here these imaging and therapeutic tools are reviewed and particularly those structures with ROS-sensitivity based on their biomedical applications and their functional groups. There is also a brief discussion about the method of preparation as well as the mechanism of action., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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 (H 2 O 2) 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. Unlabelled Image • Manganese dioxide nanoparticles are encapsulated into layer-by-layer microcapsules. • The surface charge rules the interplay between cells and microcapsules. • The antioxidant microcapsules protect cells from oxidative stress in vitro. [ABSTRACT FROM AUTHOR]