The work is published Sept. 3 in Nature Nanotechnology.

“Nanosponges are a new paradigm of treatment to block pathological molecules from triggering disease in the body,” said senior author Liangfang Zhang, a nanoengineering professor at the UC San Diego Jacobs School of Engineering. “Rather than creating treatments to block a few specific types of pathological molecules, we are developing a platform that can block a broad spectrum of them, and this way we can treat and prevent disease more effectively and efficiently.”

This work is one of the latest examples of therapeutic nanosponges developed by Zhang’s lab. Zhang, who is affiliated with the Institute of Engineering in Medicine and Moores Cancer Center at UC San Diego, and his team previously developed red blood cell nanosponges to combat and prevent MRSA infections and macrophage nanosponges to treat and manage sepsis.

The new nanosponges are nanoparticles of biodegradable polymer coated with the cell membranes of neutrophils, a type of white blood cell.

Neutrophils are among the immune system’s first responders against invading pathogens. They are also known to play a role in the development of rheumatoid arthritis, a chronic autoimmune disease that causes painful inflammation in the joints and can ultimately lead to damage of cartilage and bone tissue.

When rheumatoid arthritis develops, cells in the joints produce inflammatory proteins called cytokines. Release of cytokines signals neutrophils to enter the joints. Once there, cytokines bind to receptors on the neutrophil surfaces, activating them to release more cytokines, which in turn draws more neutrophils to the joints and so on.

The nanosponges essentially nip this inflammatory cascade in the bud. By acting as tiny neutrophil decoys, they intercept cytokines and stop them from signaling even more neutrophils to the joints, reducing inflammation and joint damage.

These nanosponges offer a promising alternative to current treatments for rheumatoid arthritis. Some monoclonal antibody drugs, for example, have helped patients manage symptoms of the disease, but they work by neutralizing only specific types of cytokines. This is not sufficient to treat the disease, said Zhang, because there are so many different types of cytokines and pathological molecules involved.

“Neutralizing just one or two types might not be as effective. So our approach is to take neutrophil cell membranes, which naturally have receptors to bind all these different types of cytokines, and use them to manage an entire population of inflammatory molecules,” said Zhang.

“This strategy removes the need to identify specific cytokines or inflammatory signals in the process. Using entire neutrophil cell membranes, we’re cutting off all these inflammatory signals at once,” said first author Qiangzhe Zhang, a Ph.D. student in Professor Liangfang Zhang’s research group at UC San Diego.

To make the neutrophil nanosponges, the researchers first developed a method to separate neutrophils from whole blood. They then processed the cells in a solution that causes them to swell and burst, leaving the membranes behind. The membranes were then broken up into much smaller pieces. Mixing them with ball-shaped nanoparticles made of biodegradable polymer fused the neutrophil cell membranes onto the nanoparticle surfaces.

“One of the major challenges of this work was streamlining this entire process, from isolating neutrophils from blood to removing the membranes, and making this process repeatable. We spent a lot of time figuring this out and eventually created a consistent neutrophil nanosponge production line,” said Qiangzhe Zhang.

In mouse models of severe rheumatoid arthritis, injecting nanosponges in inflamed joints led to reduced swelling and protected cartilage from further damage. The nanosponges performed just as well as treatments in which mice were administered a high dose of monoclonal antibodies.

The nanosponges also worked as a preventive treatment when administered prior to inducing the disease in another group of mice.

Professor Liangfang Zhang cautions that the nanosponge treatment does not eliminate the disease. “We are basically able to manage the disease. It’s not completely gone. But swelling is greatly reduced and cartilage damage is minimized,” he said.

The team hopes to one day see their work in clinical trials.

A new study uses tracking data for 14 species of migratory marine predators, from leatherback turtles to blue whales and white sharks, to show how their movements relate to the geopolitical boundaries of the Pacific Ocean. The results provide critical information for designing international cooperative agreements needed to manage these species.

“If a species spends most of its time in the jurisdiction of one or two countries, conservation and management is a much easier issue than it is for species that migrate through many different countries,” said Daniel Costa, professor of ecology and evolutionary biology at UC Santa Cruz and a coauthor of the study, published September 3 in Nature Ecology & Evolution.

“For these highly migratory species, we wanted to know how many jurisdictional regions they go through and how much time they spend in the open ocean beyond the jurisdiction of any one country,” Costa said.

Under international law, every coastal nation can establish an exclusive economic zone (EEZ) extending up to 200 nautical miles from shore, giving it exclusive rights to exploit resources and regulate fisheries within that zone. The high seas beyond the EEZs are a global commons and are among the least protected areas on Earth. Discussions have been under way at the United Nations since 2016 to negotiate a global treaty for conservation and management of the high seas.

First author Autumn-Lynn Harrison, now at the Smithsonian Conservation Biology Institute in Washington, D.C., began the study as a graduate student in Costa’s lab at UC Santa Cruz. Costa is a cofounder, with coauthor Barbara Block of Stanford University, of the Tagging of Pacific Predators (TOPP) program, which began tracking the movements of top ocean predators throughout the Pacific Ocean in 2000. Harrison wanted to use the TOPP data to address conservation issues, and as she looked at the data she began wondering how many countries the animals migrate through.

“I wanted to see if we could predict when during the year a species would be in the waters of a particular country,” Harrison said. “Some of these animals are mostly hidden beneath the sea, so being able to show with tracking data which countries they are in can help us understand who should be cooperating to manage these species.”

Harrison also began attending meetings on issues related to the high seas, which focused her attention on the time migratory species spend in these relatively unregulated waters. “Figuring out how much time these animals spend in the high seas was directly motivated by questions I was being asked by policy makers who are interested in high seas conservation,” she said.

The TOPP data set, part of the global Census of Marine Life, is one of the most extensive data sets available on the movements of large marine animals. Many of the top predators in the oceans are declining or threatened, partly because their mobility exposes them to a wide array of threats in different parts of the ocean.

Leatherback turtle populations in the Pacific could face a 96 percent decline by 2040, according to the IUCN Red List of Threatened Species, and leatherbacks are a priority species for the National Oceanic and Atmospheric Administration (NOAA). Laysan and black-footed albatrosses, both listed as near threatened on the IUCN Red List, spend most of their time on the high seas, where they are vulnerable to being inadvertently caught on long lines during commercial fishing operations.

White sharks are protected in U.S. and Mexican waters, but the TOPP data show that they spend about 60 percent of their time in the high seas. Pacific bluefin tuna, leatherback turtles, Laysan albatross, and sooty shearwaters all travel across the Pacific Ocean during their migrations.

“Bluefin tuna breed in the western North Pacific, then cross the Pacific Ocean to feed in the California Current off the United States and Mexico,” Costa said. “Sooty shearwaters not only cross the open ocean, they use the entire Pacific Ocean from north to south and go through the jurisdictions of more than 30 different countries.”

International cooperation has led to agreements for managing some of these migratory species, in some cases through regional fisheries management organizations. The Inter-American Tropical Tuna Commission (IATTC), for example, oversees conservation and management of tunas and other marine resources in the eastern Pacific Ocean.

The first session of a U.N. Intergovernmental Conference to negotiate an international agreement on the conservation of marine biological diversity beyond areas of national jurisdiction will be held in September. Harrison said she has already been asked to provide preprints and figures from the paper for this session.

“These migratory species are a shared heritage, and this paper shows their international travels better than ever before,” Harrison said. “The first step to protect them is knowing where they are over their annual cycle and promoting international agreements to manage the threats they may face across several countries.”

However, one lesser-used form of light is the terahertz (THz) region. Lying on the electromagnetic spectrum between infrared and microwaves, THz radiation does have the right frequency (around 10^12 Hz) to excite molecular vibrations. Unfortunately, its long wavelength (hundreds of micrometers) is around 100,000 times a typical molecular size, making it impossible to focus THz beams onto a single molecule by conventional optics. Only large ensembles of molecules can be studied.

Recently, a team led by The University of Tokyo’s Institute of Industrial Science (IIS) found a way around this problem. In a study in Nature Photonics, they showed that THz radiation can indeed detect the motion of individual molecules, overcoming the classical diffraction limit for focusing light beams. In fact, the method was sensitive enough to measure the tunneling of a single electron.

The IIS team showcased a nanoscale design known as a single-molecule transistor. Two adjacent metal electrodes, the source and the drain of the transistor, are placed on a thin silicon wafer in a “bowtie” shape. Then, single molecules — in this case C60, aka fullerene — are deposited in the sub-nanometer gaps between the source and drain. The electrodes act as antennas to tightly focus the THz beam onto the isolated fullerenes.

“The fullerenes absorb the focused THz radiation, making them oscillate around their center-of-mass,” explains study first-author Shaoqing Du. “The ultrafast molecular oscillation raises the electric current in the transistor, on top of its inherent conductivity.” Although this current change is minuscule — on the order of femto-amps (fA) — it can be precisely measured with the same electrodes used to trap the molecules. In this way, two vibrational peaks at around 0.5 and 1 THz were plotted.

In fact, the measurement is sensitive enough to measure a slight splitting of the absorption peaks, caused by adding or subtracting only one electron. When C60 oscillates on a metal surface, its vibrational quantum (vibron) can be absorbed by an electron in the metal electrode. Thus stimulated, the electron tunnels into the C60 molecule. The resulting negatively charged C60? molecule vibrates at a slightly lower frequency than neutral C60, thus absorbing a different frequency of THz radiation.

Apart from providing a glimpse of tunneling, the study demonstrates a practical method to obtain electronic and vibronic information on molecules that only weakly absorb THz photons. This could open up the wider use of THz spectroscopy, an under-developed method that is complementary to visible-light and X-ray spectroscopy, and highly relevant to nanoelectronics and quantum computing.

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Materials provided by Institute of Industrial Science, The University of Tokyo. Note: Content may be edited for style and length.