Tag Archives: reactive oxygen species (ROS)

Eradicating bacteria biofilm with nanocrystals

A January 8, 2021 news item on ScienceDaily announces new work from South Korea’s Pohang University of Science & Technology (POSTECH),

The COVID-19 pandemic is raising fears of new pathogens such as new viruses or drug-resistant bacteria. To this, a Korean research team has recently drawn attention for developing the technology for removing antibiotic-resistant bacteria by controlling the surface texture of nanomaterials.

A joint research team from POSTECH and UNIST [Ulsan National Institute of Science and Technology] has introduced mixed-FeCo-oxide-based surface-textured nanostructures (MTex) as highly efficient magneto-catalytic platform in the international journal Nano Letters. The team consisted of professors In Su Lee and Amit Kumar with Dr. Nitee Kumari of POSTECH’s Department of Chemistry and Professor Yoon-Kyung Cho and Dr. Sumit Kumar of UNIST’s Department of Biomedical Engineering.

Caption: Schematic diagram showing removal of bacterial biofilm via Mtex Credit: POSTECH

A January 8, 2021 POSTECH press release (also on EurkeAlert), which originated the news item, delves further,

First, the researchers synthesized smooth surface nanocrystals in which various metal ions were wrapped in an organic polymer shell and heated them at a very high temperature. While annealing the polymer shell, a high-temperature solid-state chemical reaction induced mixing of other metal ions on the nanocrystal surface, creating a number of few-nm-sized branches and holes on it. This unique surface texture was found to catalyze a chemical reaction that produced reactive oxygen species (ROS) that kills the bacteria. It was also confirmed to be highly magnetic and easily attracted toward the external magnetic field. The team had discovered a synthetic strategy for converting normal nanocrystals without surface features into highly functional mixed-metal-oxide nanocrystals.

The research team named this surface topography – with branches and holes that resembles that of a ploughed field – “MTex.” This unique surface texture has been verified to increase the mobility of nanoparticles to allow efficient penetration into biofilm matrix while showing high activity in generating reactive oxygen species (ROS) that are lethal to bacteria.

This system produces ROS over a broad pH range and can effectively diffuse into the biofilm and kill the embedded bacteria resistant to antibiotics. And since the nanostructures are magnetic, biofilm debris can be scraped out even from the hard-to-reach microchannels.

“This newly developed MTex shows high catalytic activity, distinct from the stable smooth-surface of the conventional spinel forms,” explained Dr. Amit Kumar, one of the corresponding authors of the paper. “This characteristic is very useful in infiltrating biofilms even in small spaces and is effective in killing the bacteria and removing biofilms.”

“This research allows to regulate the surface nanotexturization, which opens up possibilities to augment and control the exposure of active sites,” remarked Professor In Su Lee who led the research. “We anticipate the nanoscale-textured surfaces to contribute significantly in developing a broad array of new enzyme-like properties at the nano-bio interface.”

Here’s a link to and a citation for the paper,

Surface-Textured Mixed-Metal-Oxide Nanocrystals as Efficient Catalysts for ROS Production and Biofilm Eradication by Nitee Kumari, Sumit Kumar, Mamata Karmacharya, Sateesh Dubbu, Taewan Kwon, Varsha Singh, Keun Hwa Chae, Amit Kumar, Yoon-Kyoung Cho, and In Su Lee. Nano Lett. 2021, 21, 1, 279–287 DOI: https://doi.org/10.1021/acs.nanolett.0c03639 Publication Date: December 11, 2020 Copyright © 2020 American Chemical Society

This paper is behind a paywall.

Nanotechnology delivery system for skin disease therapies

A Feb. 29, 2016 news item on ScienceDaily announces a new development concerning free radicals that may be helpful with skin diseases and pathologies,

Researchers at The Hebrew University of Jerusalem have developed a nanotechnology-based delivery system containing a protective cellular pathway inducer that activates the body’s natural defense against free radicals efficiently, a development that could control a variety of skin pathologies and disorders.

A Feb. 29, 2016 Hebrew University of Jerusalem press release on EurekAlert, which originated the news item, expands on the theme,

The human skin is constantly exposed to various pollutants, UV rays, radiation and other stressors that exist in our day-to-day environment. When they filter into the body they can create Reactive Oxygen Species (ROS) – oxygen molecules known as Free Radicals, which are able to damage and destroy cells, including lipids, proteins and DNA.

In the skin – the largest organ of the body – an excess of ROS can lead to various skin conditions, including inflammatory diseases, pigmenting disorders, wrinkles and some types of skin cancer, and can also affect internal organs. This damage is known as Oxidative Stress.

The body is naturally equipped with defense mechanisms to counter oxidative stress. It has anti-oxidants and, more importantly, anti-oxidant enzymes that attack the ROS before they cause damage.

In a review article published in the journal Cosmetics, a PhD student from The Hebrew University of Jerusalem, working in collaboration with researchers at the Technion – Israel Institute of Technology, suggested an innovative way to invigorate the body to produce antioxidant enzymes, while maintaining skin cell redox balance – a gentle equilibrium between Reactive Oxygen Species and their detoxification.

“The approach of using the body’s own defense system is very effective. We showed that activation of the body’s defense system with the aid of a unique delivery system is feasible, and may leverage dermal cure,” said Hebrew University researcher Maya Ben-Yehuda Greenwald.

Ben-Yehuda Greenwald showed that applying nano-size droplets of microemulsion liquids containing a cellular protective pathway inducer into the skin activates the natural skin defense systems.

“Currently, there are many scientific studies supporting the activation of the body’s defense mechanisms. However, none of these studies has demonstrated the use of a nanotechnology-based delivery system to do so,” Ben-Yehuda Greenwald said.

Production of antioxidant enzymes in the body is signaled in the DNA by activation of Nrf2 – a powerful protein that exists in every cell in our body. This Nrf2 cellular-protective signaling pathway is a major intersection of many other signaling pathways affecting each other and determining cell functionality and fate. Nrf2 is capable of coordinating the cellular response to internal as well as external stressors by tight regulation of phase-II protective enzymes, such as the antioxidant enzymes.

Ben-Yehuda Greenwald has also discovered a new family of compounds capable of activating the Nrf2 pathway. Moreover, by incorporating them into the unique delivery system she has developed, she managed to efficiently stimulate the activation of the Nrf2 pathway and mimic the activity of the body’s’ natural way of coping with a variety of stress conditions.

“The formula we have created could be used in topical medication for treating skin conditions. Our formula could be used both as preventive means and for treatment of various skin conditions, such as infections, over-exposure to UV irradiation, inflammatory conditions, and also internal disease,” she said.

While the researchers focused on the skin, the formulation could prove to be effective in enhancing the body’s natural protection against the damaging effects of ROS in other parts of the body, such as inflammation in cardiovascular diseases, heart attack, cancer, multiple sclerosis and Alzheimer’s.

Here’s an image provided by Ben-Yehuda Greenwald illustrating the team’s work,

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

Caption: These are the consequences of skin exposure to stressors. Credit: Maya Ben-Yehuda Greenwald

Here’s a link to and a citation for the paper,

Skin Redox Balance Maintenance: The Need for an Nrf2-Activator Delivery System by Maya Ben-Yehuda Greenwald, Shmuel Ben-Sasson, Havazelet Bianco-Peled, and Ron Kohen. Cosmetics 2016, 3(1), 1; doi:10.3390/cosmetics3010001 Published: 15 January 2016

This paper appears to be open access.

Safer sunblock and bioadhesive nanoparticles from Yale University

The skin has a lot of protective barriers but it’s always possible to make something better so a sunblock that doesn’t penetrate the* skin at all seems like it might be a good thing. Interestingly, this new sunblock or sunscreen is enabled by nanoparticles but not the metallic nanoparticles found in what are sometimes called nanosunscreens. From a Sept. 29, 2015 news item on Nanowerk,

Researchers at Yale have developed a sunscreen that doesn’t penetrate the skin, eliminating serious health concerns associated with commercial sunscreens.

Most commercial sunblocks are good at preventing sunburn, but they can go below the skin’s surface and enter the bloodstream. As a result, they pose possible hormonal side effects and could even be promoting the kind of skin cancers they’re designed to prevent.

But researchers at Yale have developed a new sunblock, made with bioadhesive nanoparticles, that stays on the surface of the skin.

A Sept. 28, 2015 Yale University news release by William Weir, whch originated the news item, describes the research in more detail,

“We found that when we apply the sunblock to the skin, it doesn’t come off, and more importantly, it doesn’t penetrate any further into the skin,” said the paper’s senior author, Mark Saltzman, the Goizueta Foundation Professor of Biomedical Engineering. “Nanoparticles are large enough to keep from going through the skin’s surface, and our nanoparticles are so adhesive that they don’t even go into hair follicles, which are relatively open.”

Using mouse models, the researchers tested their sunblock against direct ultraviolet rays and their ability to cause sunburn. In this regard, even though it used a significantly smaller amount of the active ingredient than commercial sunscreens, the researchers’ formulation protected equally well against sunburn.

They also looked at an indirect — and much less studied — effect of UV light. When the active ingredients of sunscreen absorb UV light, a chemical change triggers the generation of oxygen-carrying molecules known as reactive oxygen species (ROS). If a sunscreen’s agents penetrate the skin, this chemical change could cause cellular damage, and potentially facilitate skin cancer.

“Commercial chemical sunblock is protective against the direct hazards of ultraviolet damage of DNA, but might not be against the indirect ones,” said co-author Michael Girardi, a professor of dermatology at Yale Medical School. “In fact, the indirect damage was worse when we used the commercial sunblock.”

Girardi, who specializes in skin cancer development and progression, said little research has been done on the ultimate effects of sunblock usage and the generation of ROS, “but obviously, there’s concern there.”

Previous studies have found traces of commercial sunscreen chemicals in users’ bloodstreams, urine, and breast milk. There is evidence that these chemicals cause disruptions with the endocrine system, such as blocking sex hormone receptors.

To test penetration levels, the researchers applied strips of adhesive tape to skin previously treated with sunscreen. The tape was then removed rapidly, along with a thin layer of skin. Repeating this procedure allowed the researchers to remove the majority of the outer skin layer, and measure how deep the chemicals had penetrated into the skin. Traces of the sunscreen chemical administered in a conventional way were found to have soaked deep within the skin. The Yale team’s sunblock came off entirely with the initial tape strips.

Tests also showed that a substantial amount of the Yale team’s sunscreen remained on the skin’s surface for days, even after exposure to water. When wiped repeatedly with a towel, the new sunblock was entirely removed. [emphasis mine]

To make the sunblock, the researchers developed a nanoparticle with a surface coating rich in aldehyde groups, which stick tenaciously to the outer skin layer. The nanoparticle’s hydrophilic layer essentially locks in the active ingredient, a hydrophobic chemical called padimate O.

Some sunscreen solutions that use larger particles of inorganic compounds, such as titanium dioxide or zinc oxide, also don’t penetrate the skin. For aesthetic reasons, though, these opaque sunscreen products aren’t very popular. By using a nanoparticle to encase padimate O, an organic chemical used in many commercial sunscreens, the Yale team’s sunblock is both transparent and stays out of the skin cells and bloodstream.

This seems a little confusing to me and I think clarification may be helpful. My understanding is that the metallic nanoparticles (nano titanium dioxide and nano zinc oxide) engineered for use in commercial sunscreens are also (in addition to the macroscale titanium dioxide and zinc oxide referred to in the Yale news release) too large to pass through the skin. At least that was the understanding in 2010 and I haven’t stumbled across any information that is contradictory. Here’s an excerpt from a July 20, 2010 posting where I featured portions of a debate between Georgia Miller (at that time representing Friends of the Earth) and Dr. Andrew Maynard (at that time director of the University of Michigan Risk Science Center and a longtime participant in the nanotechnology risk discussions),

Three of the scientists whose work was cited by FoE as proof that nanosunscreens are dangerous either posted directly or asked Andrew to post comments which clarified the situation with exquisite care,

Despite FoE’s implications that nanoparticles in sunscreens might cause cancer because they are photoactive, Peter Dobson points out that there are nanomaterials used in sunscreens that are designed not to be photoactive. Brian Gulson, who’s work on zinc skin penetration was cited by FoE, points out that his studies only show conclusively that zinc atoms or ions can pass through the skin, not that nanoparticles can pass through. He also notes that the amount of zinc penetration from zinc-based sunscreens is very much lower than the level of zinc people have in their body in the first place. Tilman Butz, who led one of the largest projects on nanoparticle penetration through skin to date, points out that – based on current understanding – the nanoparticles used in sunscreens are too large to penetrate through the skin.

However, there may be other ingredients which do pass through into the bloodstream and are concerning.

One other thing I’d like to note. Not being able to remove the sunscreen easily ( “When wiped repeatedly with a towel, the new sunblock was entirely removed.”) may prove to be a problem as we need Vitamin D, which is for the most part obtainable by sun exposure.

In any event, here’s a link to and a citation for the paper,

A sunblock based on bioadhesive nanoparticles by Yang Deng, Asiri Ediriwickrema, Fan Yang, Julia Lewis, Michael Girardi, & W. Mark Saltzman. Nature Materials (2015) doi:10.1038/nmat4422 Published online 28 September 2015

This paper is behind a paywall.

*’teh’ changed to ‘the’ on June 6, 2016.