UC San Diego nanoengineer makes Popular Science’s ‘Brilliant 10’ list

Popular Science magazine has named Liangfang Zhang, a nanoengineering professor at the University of California San Diego, in its 15^th annual “Brilliant 10” list, a lineup of “the 10 most innovative young minds in science and engineering.” Zhang was recognized for his revolutionary work in the field of nanomedicine, which focuses on nanomaterials for medical applications.

Zhang invented a way to make nanoparticles perform therapeutic tasks in the body, like treat injuries and deliver drugs to specific sites, without being rejected by the immune system. By coating nanoparticles with natural cell membranes from the body, like red blood cell membranes and platelet cell membranes, researchers can disguise nanoparticles as the body’s own cells.

“We’re essentially camouflaging nanoparticles to look and act like they belong in the body. We want to mimic the natural interaction of the body’s cells with the immune system in order to make new biomimetic nanoparticles that can safely function and survive in the body for long periods of time,” Zhang said.

Zhang’s cell membrane coating technology made its debut in a 2011 study, in which his team showed a new way to disguise nanoparticles as red blood cells. The method involved collecting the membranes from red blood cells and wrapping them around polymeric nanoparticles. This work was an important first step toward a nanodevice—for applications like drug delivery—that could circulate in the body for extended periods without being attacked by the immune system. Since red blood cells live in the body for up to 120 days, Zhang figured they would be good models and resources for making long-circulation drug delivery nanodevices.

In the 2011 study, Zhang’s team showed that nanoparticles coated with red blood cell membranes circulated in the bodies of mice for up to two days. This was an improvement over other nanoparticle systems developed for drug delivery—these are coated with a synthetic material made to temporarily suppress immune recognition and circulate in the body for just a few hours. Zhang explained that a major concern of the synthetic coating is that, after repeated use, it will eventually trigger an immune response and in the long run, these types of drug delivery systems could be drastically less effective.

Using the body’s own red blood cells marked a major breakthrough in the field of drug delivery research. Trying to mimic the most important properties of a red blood cell in a synthetic coating requires an in-depth biological understanding of how all the proteins and lipids function on the surface of a cell. It also poses what many researchers consider an insurmountable technical challenge—recreating that same cell surface precisely in the lab. But Zhang’s approach was to just take the whole surface membrane from an actual red blood cell.

“We approached this problem using an engineering shortcut and bypassed all of this fundamental biology and these technical challenges,” Zhang said. “We don’t need to fully understand exactly what is going on at the protein level. We can just take the entire cell membrane, coat it onto a nanoparticle surface, and make the nanoparticle look like a red blood cell.”

And this red blood cell disguise offers more than just extended circulation time in the body. Because red blood cells are one of the primary targets of pore-forming toxins, such as those produced by MRSA (methicillin-resistant Staphylococcus aureus), Zhang reasoned that his faux red blood cells could also serve as decoys to lure these toxins away.

Indeed, his team showed that nanoparticles coated with red blood cell membranes were capable of removing MRSA toxins from the bloodstream and as a result, also helped clear up infections caused by MRSA bacteria. This is essentially a new way to combat hard to treat bacterial infections—without the use of antibiotics, Zhang said.

Zhang describes himself as a chemical engineer with biomedical interests. He earned his bachelor’s and master’s degrees in chemical engineering at Tsinghua University in China, then earned his PhD in chemical and biomolecular engineering at the University of Illinois at Urbana Champaign, where his research focused on the fundamental science of cell membrane proteins and lipids. Afterwards, he pursued his postdoc at MIT, where his research on lipid-polymer nanoparticles for drug delivery was more applications focused.

“It felt like a natural fit to integrate my training in fundamental chemical engineering principles with biomedical applications,” Zhang said. “I see many parallels between the two fields. I think that studying the flow of nanoparticles through a blood vessel is similar, albeit more complex, to studying the flow of materials through a pipeline. They both involve knowledge of fluid dynamics, thermodynamics, and diffusion laws. Once you know all these fundamental principles, the work makes more sense.”

In 2008, Zhang became an assistant professor at UC San Diego. He was one of the first faculty recruited for the university’s newly formed Department of NanoEngineering. Shortly after, his idea to combine natural cell membranes with synthetic nanoparticles for drug delivery and other biomedical applications was born.

Over the past five years, Zhang and his lab have taken their cell membrane coating technology to new heights. They’ve disguised nanoparticles as human platelets, which have a natural affinity for binding to damaged blood vessels and certain pathogens in the body, like MRSA bacteria. Because of this affinity, platelet-mimicking nanoparticles could be used for targeted drug delivery.

Zhang’s team conducted several experiments. In one, they packed platelet membrane coated nanoparticles with a drug used to heal damaged arteries and administered them to wounded rats; in another experiment, they packed the nanoparticles with antibiotics and administered them to mice infected with MRSA bacteria. In both cases, the drugs were delivered primarily to the affected areas. “That shows the power and the promise of targeted delivery,” Zhang said.

Zhang’s team has also made disguises out of the membranes of beta cells, which are insulin-producing cells in the pancreas. They coated a nanofiber with beta cell membranes to create a pancreas-like microenvironment that encouraged beta cells to congregate, grow and produce more insulin. This work could lead to new treatments for patients with diabetes. “This is another example of mimicking natural interactions in the body to create more effective therapies,” Zhang said.

But researchers are not stopping there. Next on their list is using cell membrane coating technology to develop new systems for combating cancer tumors. Zhang is also working with several biopharmaceutical companies in San Diego to manufacture the red blood cell coated nanoparticles at large scales and get them into clinical trials.

Zhang and the rest of the “Brilliant 10” are featured in the September/October issues of Popular Science magazine and online at http://www.popsci.com/brilliant-10-2016.

Fudan University and UC San Diego hold joint nanotechnology workshop

On July 12, Fudan University and the University of California San Diego held their first joint Workshop on Nanomaterials and Nanoengineering. The event featured a full day of presentations on cutting edge nano research from UC San Diego, Fudan University and other leading research institutions in China.

“We would like to enhance the collaboration between UC San Diego and Fudan in the areas of science and engineering. This workshop will help bring on more exchanges of ideas and activities between both universities,” said Yongfeng Mei, professor of materials chemistry and physics at Fudan University and co-organizer of the event. Mei is already working with UC San Diego researchers on projects focusing on metamaterials and micro and nanomotors.

“In an effort towards future collaborations, we’re building a bridge between the leading materials program in China and the only nanoengineering department in the United States,” said Joseph Wang, distinguished professor and chair of the Department of NanoEngineering at the Jacobs School of Engineering at UC San Diego, who co-organized the event with Mei.

The joint workshop was held to honor Wang in his appointment as Honorary Professor of Fudan University. He received the honorary professorship in recognition of his pioneering contributions in nanoscience, nanomachines and nanobiotechnology.

On behalf of Fudan University, Professor Yongfeng Mei (left) and Ms. Ann Wenqing Tang, Associate Dean of International Relations (center)  present Professor Joseph Wang (right) with an Honorary Professor Award.

Joseph Wang (right) presents a UC San Diego banner to Fudan University.

At the workshop, Wang presented his lab’s work on nanomachines for medical, military, security and environmental applications. Examples include the first demonstration of nanomachines in living animals, nanomachines for cleaning up carbon dioxide pollution in water and microcannons that could fire drug-filled nanobullets at disease targets.

Other UC San Diego nanoengineering professors who gave talks at the event were:

Yi Chen

Talk title: Cell Membrane-Mediated DNA Nanostructure Formation

Description: The assembly of membrane proteins and membrane-associated proteins triggers various fundamental biological processes including cell uptake, signal transduction and inter-cellular communication. DNA nanotechnology, which enables precise control on the nanometer scale, is an alternative way to unravel such mechanisms. Chen’s lab used membrane-assisted assembly of DNA 2-D array nanostructures to mimic the pattern produced by assembly of triskelion. The successful construction of such membrane structures was confirmed by atomic force microscopy imaging.

Zhaowei Liu

Talk title: High Speed Super Resolution Microscopy

Description: Liu’s group developed high speed super resolution microscopy for various biological applications. His team demonstrated a new super resolution technique that achieves 50 nanometer wide field imaging at real movie speed.

Liangfang Zhang

Talk title: Biomimetic Nanoparticles for Drug Delivery, Detoxification and Vaccination

Description: Zhang reported on the biological functionalization of polymeric nanoparticles with a layer of membrane coating derived from natural red blood cells (RBCs). This approach aims to camouflage the nanoparticle surface with the erythrocyte exterior for long circulation while retaining the applicability of the cores that support the RBC membrane shell. In vivo results revealed superior pharmacokinetics and biodistribution by the RBC-mimicking nanoparticles compared to control particles coated with the state-of-the-art synthetic stealth materials. Three types of exciting applications of this biomimetic nanoparticle system were discussed: drug delivery, systemic detoxification and toxin vaccination.

Nanoengineers win $1 million grant to develop wearables that decontaminate chem-bio agents from skin

Nanoengineering professor Joseph Wang, lead PI

Nanoengineering professor Liangfang Zhang, co-PI

The Defense Threat Reduction Agency has awarded a $1 million grant to researchers at the Jacobs School to develop new skin-wearable systems that can rapidly and efficiently detect and remove chemical and biological agents.

The proposed wearable epidermal sensors will also be equipped with therapeutic agents that are released upon detection of the chemical and biological threats.

The project, led by nanoengineering professors Joseph Wang (director of the UC San Diego Center for Wearable Sensors) and Liangfang Zhang (faculty affiliate of the UC San Diego Institute of Engineering in Medicine), is titled "Responsive Skin-Worn Detection-Treatment System." The new research aims to provide better understanding of how chem-bio agents interact with skin tissues and builds upon recent advances from Wang and Zhang's laboratories, including epidermal electrochemical biosensors (Wang Lab) and responsive drug delivery systems (Zhang Lab).

New steroid-based eye drops clear up cataracts

Cataracts cause vision problems and blindness in tens of millions of people worldwide. So far, the only treatment is surgery. Now, new research led by opthalmogologists and engineers at UC San Diego shows a promising alternative treatment using eye drops made from a naturally occurring steroid in the human body.

Cataracts form when proteins in the eye lens, called crystallins, become malformed and clump together, clouding vision. The crystallin proteins malform either from aging, environmental factors, or genetic mutations. In this study, researchers identified a root cause for cataract formation and demonstrated a new potential remedy that doesn’t bring patients under the knife.

The team, led by Kang Zhang, a professor in the Department of Opthalmology and affiliated with the Department of NanoEngineering at UC San Diego, came up with the key ingredient for the eye drops after genetically screening children from two related families with an inherited form of cataracts. The studies revealed that these children share a genetic mutation that shuts down the production of lanosterol, a steroid that’s normally present in cataract-free eyes. With this finding, the team investigated whether lanosterol helps to prevent or clear up cataracts.

The researchers tested lanosterol on dogs with cataracts, first with an eye injection of lanosterol-loaded nanoparticles, followed by daily treatment with lanosterol eye drops. Over the course of six weeks, they observed that the cataracts in the dogs had decreased in size. The lanosterol eye drops also reduced cataracts in human lens cells and rabbit lenses, which were both grown in Petri dishes.

Dog eye lens with cataracts before lanosterol treatment (left) and after lanosterol treatment (right). Photos courtesy of Zhao et al./Nature.

NanoEngineering professor Liangfang Zhang, a co-corresponding author on the study who worked on developing the lanosterol-loaded nanoparticles, said that the researchers are aiming to move this study to clinical trials.

The findings were published in the July 30 issue of Nature.

Nanosponges offer protection against chemical weapons

Scheme depicting the detoxification of a nerve agent, DDVP, by a nanosponge, which is a red-blood-cell-coated nanoparticle (RBC-NP). Figure courtesy of Professor Liangfang Zhang and the American Chemical Society. 

These tiny particles can combat poisonous snake bites and antibiotic-resistant bacterial infections. Now, researchers show these particles can also provide protection against chemical weapons. Nanosponges developed in the lab of NanoEngineering professor Liangfang Zhang at the University of California, San Diego may one day offer a range of new life-saving treatments.

Zhang and his research group recently reported that their nanosponges increased the survival rates of mice exposed to a widely-used insecticide called DDVP, which is a toxic nerve agent. The nanosponges detoxify DDVP molecules in the blood stream by intercepting them before they attack their real targets: red blood cells. Each nanosponge is a nanoparticle coated in a red blood cell membrane. This coating lures DDVP molecules to the nanosponges and inhibits them from causing damage throughout the blood stream. The findings were published in the journal ACS Nano.

Previous studies from Zhang’s research group have demonstrated that nanosponges are also effective at removing a variety of other harmful toxins from the blood stream, such as those produced by MRSA bacteria, E. coli, snake bites and bee stings.

Read more about nanosponges here.