Tunable coating allows hitch-hiking nanoparticles to slip past the immune system to their target
Nanoparticles are promising drug delivery tools, offering the ability to administer drugs directly to a specific part of the body and avoid the awful side effects so often seen with chemotherapeutics.
But there’s a problem. Nanoparticles struggle to get past the immune system’s first line of defense: proteins in the blood serum that tag potential invaders. Because of this, only about 1 percent of nanoparticles reach their intended target.
“No one escapes the wrath of the serum proteins,” said Eden Tanner, a former postdoctoral fellow in bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).
Now, Tanner and a team of researchers led by Samir Mitragotri, the Hiller Professor of Bioengineering and Hansjorg Wyss Professor of Biologically Inspired Engineering at SEAS, have developed an ionic forcefield that prevents proteins from binding to and tagging nanoparticles.
In mouse experiments, nanoparticles coated with the ionic liquid survived significantly longer in the body than uncoated particles and, surprisingly, 50 percent of the nanoparticles made it to the lungs. It’s the first time that ionic liquids have been used to protect nanoparticles in the blood stream.
“The fact that this coating allows the nanoparticles to slip past serum proteins and hitch a ride on red blood cells is really quite amazing because once you are able to fight the immune system effectively, lots of opportunities open up,” said Mitragotri, who is also a Core Faculty Member of Harvard’s Wyss Institute for Biologically Inspired Engineering
The research is published in Science Advances.
Ionic liquids, essentially liquid salts, are highly tunable materials that can hold a charge.
“We knew that serum proteins clear out nanoparticles in the bloodstream by attaching to the surface of the particle and we knew that certain ionic liquids can either stabilize or destabilize proteins,” said Tanner, who is now an Assistant Professor of Chemistry & Biochemistry at the University of Mississippi. “The question was, could we leverage the properties of ionic liquids to allow nanoparticles to slip past proteins unseen.”
“The great thing about ionic liquids is that every small change you make to their chemistry results in a big change in their properties,” said Christine Hamadani, a former graduate student at SEAS and first author of the paper. “By changing one carbon bond, you can change whether or not it attracts or repels proteins.”
Hamadani is currently a graduate student at Tanner’s lab at the University of Mississippi.
The researchers coated their nanoparticles with the ionic liquid choline hexenoate, which has an aversion to serum proteins. Once in the body, these ionic-liquid coated nanoparticles appeared to spontaneously attach to the surface of red-blood cells and circulate until they reached the dense capillary system of the lungs, where the particles sheared off into the lung tissue.
“This hitchhiking phenomenon was a really unexpected discovery,” said Mitragotri. “Previous methods of hitchhiking required special treatment for the nanoparticles to attach to red blood cells and even then, they only stayed at a target location for about six hours. Here, we showed 50 percent of the injected dose still in the lungs after 24 hours.”
The research team still needs to understand the exact mechanism that explains why these particles travel so well to lung tissue, but the research demonstrates just how precise the system can be.
“This is such a modular technology,” said Tanner, who plans to continue the research in her lab at University of Mississippi. “Any nanoparticle with a surface change can be coated with ionic liquids and there are millions of ionic liquids that can be tuned to have different properties. You could tune the nanoparticle and the liquid to target specific locations in the body.”
“We as a field need as many tools as we can to fight the immune system and get drugs where they need to go,” said Mitragotri. “Ionic liquids are the latest tool on that front.”
The research was co-authored by Morgan J. Goetz.
Breakthrough in understanding ‘tummy bug’ bacteria
Scientists have discovered how bacteria commonly responsible for seafood-related stomach upsets can go dormant and then “wake up”.
Vibrio parahaemolyticus is a marine bacterium that can cause gastroenteritis in humans when eaten in raw or undercooked shellfish such as oysters and mussels.
Some of these bacteria are able to turn dormant in poor growth conditions such as cold temperatures – and can remain in that state of hibernation for long periods before resuscitating.
University of Exeter scientists have identified a population of these dormant cells that are better at waking up, and have discovered an enzyme involved in that waking up process.
“Most of these bacteria die when they encounter poor growth conditions, but we identified sub-populations of bacteria that are able to stay dormant for long periods of time,” said lead author Dr Sariqa Wagley, of the University of Exeter.
“We found that this population has a better ability to revive when conditions improve.
“Our tests show that when these dormant bacteria are revived they are just as virulent and able to cause disease.”
The findings could have implications for seafood safety, as dormant cells are not detectable using routine microbiological screening tests and the true bacterial load (amount of bacteria) could be underestimated.
“When they go dormant, these bacteria change shape, reduce respiration activities and they don’t grow like healthy bacteria on agar plates used in standard laboratory tests, so they are much harder to detect,” Dr Wagley explained.
“Using a range of tools, we were able to find dormant bacteria in seafood samples and laboratory cultures and look at their genetic content to look for clues in how they might survive for long periods.
“It is important to note that thorough cooking kills bacteria in seafood.
“Our results may also help us predict the conditions that dormant bacteria need in order to revive.”
Working with the seafood industry, the Exeter team identified a lactate dehydrogenase enzyme that breaks down lactic acid into pyruvate, a key component of several metabolic pathways (chemical reactions in a cell).
The findings suggest that lactate dehydrogenase is essential both for maintaining bacterial dormancy and resuscitation back to an active form.
Vibrio parahaemolyticus usually grows in warm and tropical marine environments, although Dr Wagley said that due to rising sea temperatures in recent years it is now prevalent in UK waters during the summer months.
During the winter, it is not detected in the marine environment around the UK and it is thought to die due to the cold winter temperatures.
This study could explain how Vibrio parahaemolyticus is able remerge in the environment during the summer.
The study was partly funded by the Biotechnology and Biological Sciences Research Council (BBSRC), with additional funding and support from Lyons Seafoods.
The paper, published in the journal PLOS Pathogens, is entitled: “Bacterial dormancy: a subpopulation of viable but non-culturable cells demonstrates better fitness for revival.”
Stealing the spotlight in the field and kitchen
January 20, 2021 – Plant breeders are constantly working to develop new bean varieties to meet the needs and desires of the food industry. But not everyone wants the same thing.
Many consumers desire heirloom-type beans, which have great culinary quality and are visually appealing. On the other hand, farmers desire beans with better disease resistance and higher yield potential.
The bean varieties that farmers want to grow are usually different than the varieties consumers want to purchase. Until now.
Travis Parker, a plant scientist at University of California, Davis, has worked with a team of researchers to release five new varieties of dry beans that combine the most desirable traits.
The new varieties, UC Sunrise, UC Southwest Red, UC Tiger’s Eye, UC Rio Zape, and UC Southwest Gold, were recently highlighted in the Journal of Plant Registrations, a publication of the Crop Science Society of America.
“Our new beans combine the best of both worlds for farmers and consumers,” says Parker. “They combine the better qualities of heirloom-type beans with the better qualities of commercial types.”
Heirloom-type beans often represent older bean types that are known for culinary qualities and seed patterns. These are highly desired by consumers. Heirloom types often fetch a higher market value than other beans.
Commercial dry beans often have higher yields, shorter maturity times, and improved disease resistance. While they possess qualities desirable to producers, they don’t fetch as high of a market price compared to their heirloom counterparts.
“Our goal was to improve field characteristics of the heirloom beans without losing culinary characteristics,” said Parker. “We have an interest in higher-value varieties and want them to grow well.”
Farmers growing the heirloom dry beans often sell the beans to health-conscious consumers or high-end restaurants. This sale often leads to a higher price point. However, these beans are prone to disease and don’t perform well in the field.
“We know that existing heirloom beans don’t usually do well in terms of yield,” said Parker. “Breeding beans for high yields is a major improvement for farmers. The new varieties are high-yielding, heat-tolerant, and are also resistant to bean common mosaic virus.”
Incorporating disease resistance was essential when developing the new bean varieties. Bean common mosaic virus is a well-known problem that is hard to control in the field.
“The only real effective means to handle the virus is through genetic resistance,” explains Parker.
The new varieties, such as UC Sunrise, satisfy the need for farmers to have a bean that is disease resistant while also yielding 50% more than heirloom types. In addition, the beans do not take as long to grow between planting and harvest.
Commercial and heirloom beans come from the same species, but they are in different market classes. The heirloom varieties are bred with intimate knowledge of what tastes good and what works well in the kitchen.
“In recent decades, there has been less attention paid to consumer desires during the bean breeding process,” says Parker. “There are more layers between the breeder and the consumer. We are trying to make sure to keep consumers in mind while incorporating qualities that are beneficial to the farmer.”
With consumer desires in mind, the research team used cross-pollination to breed plants with key characteristics they selected. As Parker and the team continued the breeding process, they performed taste tests to ensure the beans met the level of culinary quality expected of an heirloom-type bean, in terms of flavor and visual appeal.
This research was supported by the Clif Bar Family Foundation, Lundberg Family Farms, the United States Department of Agriculture Organic Agriculture Research & Extension Initiative, and the United States Department of Agriculture Western Sustainable Agriculture Research and Education program.
American Society of Agronomy, Soil Science Society of America, Crop Science Society of America: Collectively, these Societies represent more than 12,000 individual members around the world. Members are researchers and professionals in the areas of growing our world’s food supply while protecting our environment. Together we work toward solutions to advance scientific knowledge in the areas of agronomy, crop science, and soil science.
Twitter: @ASA_CSSA_SSSA & @SSSA_soils | Instagram: @sustainablefoodsupply & @iheartsoil
Genome editing to treat human retinal degeneration
New Rochelle, NY, January 19, 2021–Gene editing therapies, including CRISPR-Cas systems, offer the potential to correct mutations causing inherited retinal degenerations, a leading cause of blindness. Technological advances in gene editing, continuing safety concerns, and strategies to overcome these challenges are highlighted in the peer-reviewed journal Human Gene Therapy. Click here to read the full-text article free on the Human Gene Therapy website.
“Currently, the field is undergoing rapid development with a number of competing gene editing strategies, including allele-specific knock-down, base editing, prime editing, and RNA editing, are under investigation. Each offers a different balance of on-target editing efficiency versus off-target risks,” state Kanmin Xue, University of Oxford, and coauthors. “Testing these newly-developed CRISPR technologies in human retinal tissue, organoids and in vivo will help to highlight the most-viable therapeutic approaches for treating inherited retinal diseases in the future.”
Characterizing the rapidly evolving field of CRISPR-Cas based genome editing and current strategies for extending the capabilities of CRISPR-Cas9, the article also features epigenetic editing, the risks of retinal gene editing, and approaches in development to control Cas9 activity and improve safety.
“The eye is an ideal target for in vivo gene editing. Dr. Xue’s review provides an excellent overview of the current state of the art,” says Editor-in-Chief of Human Gene Therapy Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Dep
uty Chancellor, University of Massachusetts Medical School.
About the Journal
Human Gene Therapy, the Official Journal of the European Society of Gene and Cell Therapy and eight other international gene therapy societies, was the first peer-reviewed journal in the field and provides all-inclusive access to the critical pillars of Human Gene Therapy: research, methods, and clinical applications. The Journal is led by Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, and an esteemed international editorial board. Human Gene Therapy is available in print and online. Complete tables of contents and a sample issue are available on the Human Gene Therapy website.
About the Publisher
Mary Ann Liebert, Inc., publishers is known for establishing authoritative peer-reviewed journals in many promising areas of science and biomedical research. Its biotechnology trade magazine, GEN (Genetic Engineering & Biotechnology News), was the first in its field and is today the industry’s most widely read publication worldwide. A complete list of the firm’s 90 journals, books, and newsmagazines is available on the Mary Ann Liebert, Inc., publishers website.
Protected areas vulnerable to growing emphasis on food security
New study shows croplands are prevalent in protected areas, challenging their efficacy in meeting conservation goals
Protected areas are critical to mitigating extinction of species; however, they may also be in
conflict with efforts to feed the growing human population. A new study shows that 6% of all
global terrestrial protected areas are already made up of cropland, a heavily modified habitat
that is often not suitable for supporting wildlife. Worse, 22% of this cropland occurs in areas
supposedly enjoying the strictest levels of protection, the keystone of global biodiversity
This finding was published in the Proceedings of the National Academy of Sciences by
researchers at the University of Maryland’s National Socio-Environmental Synthesis Center
(SESYNC) and National Institute for Mathematical and Biological Synthesis ( NIMBioS ) at the
University of Tennessee. In order to comprehensively examine global cropland impacts in
protected areas for the first time, the authors synthesized a number of remotely sensed
cropland estimates and diverse socio-environmental datasets.
The persistence of many native species–particularly habitat specialists (species that depend on
a narrow set of natural systems), rare, and threatened species–is incompatible with conversion
of habitat to cropland, thus compromising the primary conservation goal of these protected
areas. Guided by the needs of conservation end users, the researchers used methods that
provide an important benchmark and reproducible methods for rapid monitoring of cropland in
“Combining multiple remote sensing approaches with ongoing inventory and survey work will
allow us to better understand the impacts of conversion on different taxa,” says lead author
Varsha Vijay, a conservation scientist who was a postdoctoral fellow at SESYNC while working
on the study. “Cropland in biodiversity hotspots warrant particularly careful monitoring. In many
of these regions, expanding cropland to meet increasing food demand exposes species to both
habitat loss and increased human-wildlife conflict,” she adds.
Countries with higher population density, lower income inequality, and higher agricultural
suitability tend to have more cropland in their protected areas. Even though cropland in
protected areas is most dominant in mid-northern latitudes, the tradeoffs between biodiversity
and food security may be most acute in the tropics and subtropics. This increased tradeoff is
due to higher levels of species richness coinciding with a high proportion of cropland-impacted
“The findings of this study emphasize the need to move beyond area-based conservation
targets and develop quantitative measures to improve conservation outcomes in protected
areas, especially in areas of high food insecurity and biodiversity” says Lucas Joppa, chief
environmental officer of Microsoft, who has published numerous papers on the topic of
protected area effectiveness but who was not an author on the study.
2021 is a historic “Year of Impact,” when many countries and international agencies are
developing new decadal targets for biodiversity conservation and protected areas. As countries
aim to meet these goals and the 2030 Sustainable Development Goals, there is an increasing
need to understand synergies and tradeoffs between these goals in order to ensure a more
sustainable future. Studies such as these offer insights for protected area planning and
management, particularly as future protected areas expand into an agriculturally dominated
matrix. Though the study reveals many challenges for the future, it also reveals potential
scenarios for restoration in mid-northern latitudes and for cooperation between conservation
and food programs in regions with both high levels of food insecurity and biodiversity.
“Despite clear connections between food production and biodiversity, conservation and
development planning are still often treated as independent processes,” says study co-author
Paul Armsworth from the University of Tennessee. “Rapid advances in data availability provide
exciting opportunities for bringing the two processes together,” adds Vijay.
The paper, “Pervasive cropland in protected areas highlight trade-offs between conservation
and food security,” Varsha Vijay and Paul Armsworth, appears in the Proceedings of the
National Academy of Sciences. doi:10.1073/pnas.2010121118
The study is based upon work funded by the National Science Foundation (Award No.: DBI-
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