Testing nanomedicine in space

(Nanowerk Spotlight) In chemistry, free radicals are atomic or molecular species with unpaired electrons on an otherwise open shell configuration. These unpaired electrons are usually highly reactive, so radicals are likely to take part in chemical reactions. Free radicals can damage components of a cells' membranes, proteins or genetic material by oxidizing them – the same chemical reaction that causes iron to rust. This is called oxidative stress (OS).
Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy. Oxidative stress also is believed to play a role in neurodegenerative diseases such as Alzheimer's and Parkinson's.
In order to counteract intracellular damage by free radicals, cells have developed a so-called intracellular antioxidant system. This process transforms free electrons into a nonreactive form by proteins (enzymes).
In addition, the external supply of antioxidant agents is a common strategy for OS prevention and treatment. Here, nanotechnology has provided dramatic improvement in controlling or eliminating biological oxidation reactions. This may provide a new basis for pharmacological treatment of diseases related to oxidative stress (read more: "Radical nanotechnology – how medicine can learn from materials science".
Three of the most-studied nanoparticle redox reagents, at the cellular level, are fullerenes, carbon nanotubes and rare earth oxide nanoparticles (particularly cerium, i.e. nanoceria).
"Conditions that decrease gravity load for several days or weeks, such as prolonged bed rest or long space flights, cause the deterioration and weakening of the postural muscles, and this phenomenon has been shown to be tightly correlated with oxidative stress," Gianni Ciofani, an Associate Professor at Polytechnic University of Torino and the Principal Investigator of the Smart Bio-Interfaces group at the Italian Institute of Technology, tells Nanowerk. "This inspired us to investigate the potentially protective role of nanoceria against oxidative stress associated with microgravity and cosmic radiations in space."
Ciofani and his team tested nanoceria as antioxidant in skeletal muscle cells during their maturation process (differentiation) under different gravity levels, obtained by culture on Earth and aboard the International Space Station (ISS) during the Italian Space Agency Biomission Vita (NANOROS project, 2016-7-U.0).
Their findings have been published in Nanomedicine ("Modulation of gene expression in rat muscle cells following treatment with nanoceria in different gravity regimes").
Muscle cells were cultured in the depicted fluidic systems and exposed to cerium oxide nanoparticles under both microgravity and normal gravity. After three days, the samples were fixed. Upon return to Earth, both space and ground samples were analyzed with microarrays for generating heat maps, Venn diagrams and gene ontology plots. (Image: Istituto Italiano di Tecnologia) (click on image to enlarge)
"Our findings support the application of antioxidant nanomaterials to skeletal muscle tissue culture for protection from the noxious effects of microgravity and cosmic radiations, which result in muscle mass and force loss and limit human operations and permanence in space," says Giada Genchi, a Post-Doctoral Fellow in Ciofani's group and the paper's first author. "On Earth, these deteriorations are usually associated with aging or pathologies and are exhibited over longer time intervals compared to those occurring in space. This makes our experiment predictive of the possible efficacy of antioxidant nanomaterials based on nanoceria in the treatment of several musculodegenerative conditions."
Most importantly, nanoceria promotes the transcription of genes (Lmna and H2afx) associated with DNA protection from oxidative stress. These genes are also involved in a number of common metabolic processes, such as aging or adipogenesis. Their alteration is known to cause degenerative diseases.
By endowing nanoparticles with self-regenerative biomimetic antioxidant effects, the scientists' goal is to achieve a reduction of OS, thereby minimizing its negative impact on skeletal muscle building blocks (contractile proteins, DNA etc.) both on Earth and in space.
"Our work encourages further studies on nanomaterials in microgravity for the promotion of extended human space travel, as well as for the identification of suitable biomedical protocols for the treatment of conditions typically associated to aging and disease on Earth," Genchi points out. "Besides shedding light on the protective role of nanoceria against microgravity and space radiation induced OS, it should also motivate the scientific community to investigate in-depth nanomaterial interaction with biological matter in microgravity."
The team's present study will be complemented by another study on skeletal muscle cell proliferation under the same conditions, aiming at elucidating the role of these antioxidants in different stages of life of the skeletal muscle cell. Another experiment with skeletal muscle cells and nanoceria will be performed aboard the ISS in 2019, and transcriptomic analyses will be validated by accurate investigations on gene promoters, as well as on gene products.
According to the team, a number of future studies should address 1) the targeting of nanoceria to specific anatomical sites; 2) the administration routes of antioxidant nanoparticles (food supplement, systemic etc.); 3) long-term fate and effect of the nanoparticles in the intact organism level; and 4) the molecular underpinnings of the therapeutic effects of nanoceria.
One of the main challenges in this research field is the uncertain future of the ISS after 2020. This poses the need for a stronger international cooperation for the access to new real microgravity platforms, as well as to simulated microgravity facilities on Earth able to reproduce also highly energetic cosmic radiations.
By Michael is author of two books by the Royal Society of Chemistry: Nano-Society: Pushing the Boundaries of Technology and Nanotechnology: The Future is Tiny. Copyright © Nanowerk

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