Advanced nanozymes for antioxidant therapy

Oxidative stress is a well-known issue, which affects astronauts during spaceflights. The use of innovative and more effective antioxidant agents is thus under intensive investigation. In this framework, some nanomaterials able to mimic antioxidant enzymes are emerging as promising candidates as innovative therapeutics. Such artificial enzymes (also called nanozymes) are, in fact, being explored in several contexts related to space missions and zero gravity environment due to their superior stability and long-term activity, including current investigations on ceria nanoparticles by ESA and NASA. Moreover, a promising biocompatible nanomaterial (platinum nanospheres) with precisely controlled physical-chemical characteristics and strong and broad antioxidant potential (simultaneous HRP-SOD-CAT enzymes mimics) is currently under investigation in a project funded by Italian Space Agency (ASI).

The aim of this project is to develop new antioxidant agents to counteract oxidative stress problems during space missions. In particular, our main objective is to achieve a strong improvement of the therapeutic effects of nanozymes in terms of efficiency and selectivity, by investigating the next generation of nanozymes, such as shape-controlled nanozymes with controlled surface structure at nanoscale, a crucial parameter in catalytic processes. In this framework, we are developing a broad sub-10 nm nanozyme library (e.g., platinum octahedral nanocrystals, porous platinum nanoparticles, palladium nanocubes/nanorods, nanospheres, etc, with different sizes.) with “naked” surface and highly controlled crystallographic surface structures. Such unique features will allow us to deepen the understanding of these promising antioxidant agents, increasing their efficiency and selectivity in cellular processes.

To this purpose, we are performing systematic in vitro and in vivo investigations, analyzing the cellular and molecular mechanisms of the antioxidant activity of nanozymes and their efficacy in counteracting degenerative processes induced by oxidative stress. The antioxidant function of nanozymes is analyzed in human cell lines, primary neurons or human neurons reprogrammed by induced pluripotent stem cells (iPSCs) by evaluating: (i) the mechanisms of cellular uptake and the intracellular fate of nanozymes; (ii) their ability in decreasing endogenous reactive oxygen species (ROS) levels and their overproduction after external oxidative insults of various degree (hypoxia, strong oxidants, radiation); (iii) their effects on neuronal survival and on biomarkers of neurodegeneration; (iv) the duration of their action over time, and (v) their ability to pass the blood-brain barrier (BBB). The activity of nanozymes will be analysed also under microgravity conditions, using the Airbus Random Positioning Machine 2.0, which allows to grow cells under controlled environment of reduced gravity. This will enable us to reproduce and test, in vitro, the advantages and limitations of the possible future use of these nanodevices during spaceflights. The most effective nanozymes will be investigated in vivo for their ability to counteract neuronal degeneration. We will use rat and mouse models of retinal photoreceptor degeneration triggered by (i) genetic mutations in photoreceptor or pigment epithelium genes; (ii) toxic agents such as iodoacetic acid; (iii) damage by acute exposure to intense light.

Project funding: European Space Agency (ESA)