Tag Archives: Peng Zhang

Nanomaterial shapes and forms affect passage through blood brain barrier (BBB)

I meant to get this published a lot sooner.

There seems to be a lot of excitement about this research. I got an embargoed press release further in advance than usual and now the embargo is lifted, it’s everywhere except, at the time of this writing (0920 PDT July 6, 2021), on the publisher’s (Proceedings of the National Academy of Sciences [PNAS]) website.

A July 5, 2021 news item on Medical Express announces the news,

Nanomaterials found in consumer and health-care products can pass from the bloodstream to the brain side of a blood-brain barrier model with varying ease depending on their shape—creating potential neurological impacts that could be both positive and negative, a new study reveals.

A July 5, 2021 University of Birmingham press release (also on EurekAlert), which originated the news item, delves into the details,

Scientists found that metal-based nanomaterials such as silver and zinc oxide can cross an in vitro model of the ‘blood brain barrier’ (BBB) as both particles and dissolved ions – adversely affecting the health of astrocyte cells, which control neurological responses.

But the researchers also believe that their discovery will help to design safer nanomaterials and could open up new ways of targeting hard-to-reach locations when treating brain disease.

Publishing its findings today in PNAS, an international team of researchers discovered that the physiochemical properties of metallic nanomaterials influence how effective they are at penetrating the in vitro model of the blood brain barrier and their potential levels of toxicity in the brain.

Higher concentration of certain shapes of silver nanomaterials and zinc oxide may impair cell growth and cause increased permeability of the BBB, which can lead to the BBB allowing easier brain access to these compounds.

The BBB plays a vital role in brain health by restricting the passage of various chemical substances and foreign molecules into the brain from surrounding blood vessels.

Impaired BBB integrity compromises the health of the central nervous system and increased permeability to foreign substances may eventually cause damage to the brain (neurotoxicity).

Study co-author Iseult Lynch, Professor of Environmental Nanosciences at the University of Birmingham, commented: “We found that silver and zinc oxide nanomaterials, which are widely used in various daily consumer and health-care products, passed through our in vitro BBB model, in the form of both particles and dissolved ions.

“Variation in shape, size and chemical composition can dramatically influence nanomaterials penetration through the (in vitro) blood brain barrier. This is of paramount importance for tailored medical application of nanomaterials – for example targeted delivery systems, bioimaging and assessing possible risks associated with each type of metallic nanomaterial.”

The BBB is a physical barrier composed of a tightly packed layer of endothelial cells surrounding the brain which separates the blood from the cerebrospinal fluid allowing the transfer of oxygen and essential nutrients but preventing the access of most molecules.

Recent studies found nanomaterials such as zinc oxide can accumulate on the brain side of the in vitro BBB in altered states which can affect neurological activity and brain health. Inhaled, ingested, and dermally-applied nanomaterials can reach the blood stream and a small fraction of these may cross the BBB – impacting on the central nervous system.

The researchers synthesised a library of metallic nanomaterials with different particle compositions, sizes, and shapes – evaluating their ability to penetrate the BBB using an in vitro BBB model, followed by assessment of their behaviour and fate in and beyond the model BBB.

Co-author Zhiling Guo, a Research Fellow at the University of Birmingham, commented: “”Understanding these materials’ behaviour once past the blood brain barrier is vital for evaluating the neurological effects arising from their unintentional entry into the brain. Neurotoxicity potential is greater in some materials than others, due to the different ways their shapes allow them to move and be transported.”

The research team tested varied sizes of cerium oxide and iron oxide, along with zinc oxide and four different shapes of silver – spherical (Ag NS), disc-like (Ag ND), rod-shaped (Ag NR) and nanowires (Ag NW).

Zinc oxide slipped through the in vitro BBB with the greatest ease. The researchers found spherical and disc-like silver nanomaterials underwent different dissolution regimes – gradually transforming to silver-sulfur compounds within the BBB, creating ‘easier’ entry pathways.

Zinc oxide is used as a bulking agent and a colorant. In over-the-counter drug products, it is used as a skin protectant and a sunscreen – reflecting and scattering UV radiation to help reduce or prevent sunburn and premature aging of the skin. Silver is used in cosmetic and skincare products such as anti-aging creams.

There’s still a long way to go with this research. For anyone who’s unfamiliar with the term ‘in vitro’, the rough translation is ‘in glass’ meaning test tubes, petri dishes, etc. are used. Even though the research paper has been peer-reviewed (not a perfect process), once it becomes available there will be added scrutiny from scientists with regard to how the research was conducted and whether or not the conclusions drawn are reasonable. One more question should also be asked, are the results reproducible by other scientists?

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

Biotransformation modulates the penetration of metallic nanomaterials across an artificial blood–brain barrier model by Zhiling Guo, Peng Zhang, Swaroop Chakraborty, Andrew J Chetwynd, Fazel Abdolahpur Monikh, Christopher Stark, Hanene Ali-Boucetta, Sandra Wilson, Iseult Lynch, and Eugenia Valsami-Jones. PNAS 118 (28) e2105245118 DOI: https://doi.org/10.1073/pnas.2105245118 Published: July 13, 2021

This paper appears to be open access.

Research into nanosilver’s antibiotic properties and nanogold’s detection skills

There is a puzzling and exciting announcement from the Canadian Light Source in a May 27, 2015 news item on Nanowerk,

Precious metals like silver and gold have biomedical properties that have been used for centuries, but how do these materials effectively combat the likes of cancer and bacteria without contaminating the patient and the environment?

These are the questions that researchers from Dalhousie University and the Canadian Light Source are trying to find out.

Perhaps I’m misreading the announcement but the statement that nanosilver and nanogold don’t contaminate the patient or the environment is a bit exuberant. There are published studies examining questions about whether or not nanosilver may affect the environment and health and the answer is that no one is certain yet. You can read more about two studies highlighted in my February 28, 2013 posting titled:  Silver nanoparticles, water, the environment, and toxicity. As for nanosilver and nanogold not contaminating patients, that too is a problematic statement. For example, I have this paper which cites several studies on nanogold and possible toxicity. The paper itself is a plea to standardize testing and protocols so researchers can do a better job of establishing toxicity issues with nanogold.

GoldNP_ToxicityMar2015

Reservations aside, it’s good to learn of some Canadian research in this area. From a May 26, 2015 Canadian Light Source news release, which originated the news item, provides more details about the research and its current focus on nanosilver,

“Gold and silver are both exciting materials,” said Peng Zhang, Associate Professor of Chemistry at Dalhousie. “We can use gold to either detect or kill cancer cells. Silver is also excited and a very promising material as an antibacterial agents.”

Zhang said that if you compare silver to current antibiotics, silver does not show drug-resistant behaviour. “But with silver, so far, we are not finding that,” he added.

Finding out why silver is such a great antibacterial agent is the focus of Zhang’s research, recently published in the journal Langmuir.

“We want to understand the relationship between the atomic structure and bioactivity of nanosilver as to why it is so efficient at inhibiting bacterial activity. It’s a big puzzle.”

Zhang said it is very hard to understand what is happening at the atomic level. Using small nanosilver particles is the most effective way, because when you make silver small, you can expect higher activity because of the increased surface area.

This poses another problem however, as the nanosilver needs to be stabilized with a coating or the silver particles will bond together forming large pieces of silver that do not efficiently interact with the bacteria.

Zhang’s group used two different coatings to compare the effectiveness of the silver as an antibacterial agent. The first was a small amino acid coating and the other was a larger polymer coating. And after testing the interactions between the nanosilver and the bacteria, and looking at the atomic structure of nanosilver using the CLS and the Advanced Photon Source, the researchers were surprised to find that the thicker, larger polymer coating actually created a better delivery method for sliver to inhibit the bacteria.

“We proposed that the small amino acid coating would bind so tightly to the silver surface that it would be difficult for  the silver atoms to interact with the bacteria, whereas the polymers are actually very good at staying in place and still releasing sufficient amount of silver with the bacteria.”

Zhang said the next steps will be to find out if the nanosilver is actually attacking good cells in living systems before they can make any further progress on determining whether nanosilver is an effective and efficient antibactieral agent that could be used to cure human and animal diseases.

Here’s an illustration provided by the researchers,

The atomic structure of nanosilver, revealed by synchrotron X-ray spectroscopy, is proving to be a determinant of silver’s antibacterial activity. Padmos, J. Daniel, et al. "Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles." Langmuir 31.12 (2015): 3745-3752.

The atomic structure of nanosilver, revealed by synchrotron X-ray spectroscopy, is proving to be a determinant of silver’s antibacterial activity.
Padmos, J. Daniel, et al. “Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles.” Langmuir 31.12 (2015): 3745-3752.

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

Impact of Protecting Ligands on Surface Structure and Antibacterial Activity of Silver Nanoparticles by J. Daniel Padmos, Robert T. M. Boudreau, Donald F. Weaver, and Peng Zhang. Langmuir, 2015, 31 (12), pp 3745–3752
DOI: 10.1021/acs.langmuir.5b00049 Publication Date (Web): March 15, 2015

Copyright © 2015 American Chemical Society

This paper is behind a paywall.

Purple promises and bioimaging from Singapore’s A*STAR

A May 7, 2014 news item on Nanowerk describes a promising new approach to bioimaging,

Labeling biomolecules with light-emitting nanoparticles is a powerful technique for observing cell movement and signaling under realistic, in vivo conditions. The small size of these probes, however, often limits their optical capabilities. In particular, many nanoparticles have trouble producing high-energy light with wavelengths in the violet to ultraviolet range, which can trigger critical biological reactions.

Now, an international team led by Xiaogang Liu from the A*STAR Institute of Materials Research and Engineering and the National University of Singapore has discovered a novel class of rare-earth nanocrystals that preserve excited energy inside their atomic framework, resulting in unusually intense violet emissions …

A May 7, 2014 A*STAR (Agency for Science, Technology and Research) news release (h/t Imagist), which originated the news item, describes the problems with current bioimaging techniques and the new approach in more detail (Note: Links have been removed)

Nanocrystals selectively infused, or ‘doped’, with rare-earth ions have attracted the attention of researchers, because of their low toxicity and ability to convert low-energy laser light into violet-colored luminescence emissions — a process known as photon upconversion. Efforts to improve the intensity of these emissions have focused on ytterbium (Yb) rare-earth dopants, as they are easily excitable with standard lasers. Unfortunately, elevated amounts of Yb dopants can rapidly diminish, or ‘quench’, the generated light.

This quenching probably arises from the long-range migration of laser-excited energy states from Yb and toward defects in the nanocrystal. Most rare-earth nanocrystals have relatively uniform dopant distributions, but Liu and co-workers considered that a different crystal arrangement — clustering dopants into multi-atom arrays separated by large distances — could produce localized excited states that do not undergo migratory quenching.

The team screened numerous nanocrystals with different symmetries before discovering a material that met their criteria: a potassium fluoride crystal doped with Yb and europium rare earths (KYb2F7:Eu). Experiments revealed that the isolated Yb ‘energy clusters’ inside this pill-shaped nanocrystal (see image) enabled substantially higher dopant concentrations than usual — Yb accounted for up to 98 per cent of the crystal’s mass — and helped initiate multiphoton upconversion that yielded violet light with an intensity eight times higher than previously seen.

The researchers then explored the biological applications of their nanocrystals by using them to detect alkaline phosphatases, enzymes that frequently indicate bone and liver diseases. When the team brought the nanocrystals close to an alkaline phosphate-catalyzed reaction, they saw the violet emissions diminish in direct proportion to a chemical indicator produced by the enzyme. This approach enables swift and sensitive detection of this critical biomolecule at microscale concentration levels.

“We believe that the fundamental aspects of these findings — that crystal structures can greatly influence luminescence properties — could allow upconversion nanocrystals to eventually outperform conventional fluorescent biomarkers,” says Liu.

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

Enhancing multiphoton upconversion through energy clustering at sublattice level by Juan Wang, Renren Deng, Mark A. MacDonald, Bolei Chen, Jikang Yuan, Feng Wang, Dongzhi Chi, Tzi Sum Andy Hor, Peng Zhang, Guokui Liu, Yu Han, & Xiaogang Liu. Nature Materials 13, 157–162 (2014) doi:10.1038/nmat3804 Published online 24 November 2013

This paper is behind a paywall but there is a free preview via ReadCube Access.