Clip from NanoXpo 2018: Yao Jiang

Yao Jiang, a grad student in Prof. Liangfang Zhang’s lab, is making nanoparticles that can “train the immune system to fight cancer.” These nanoparticles are coated in the membranes of cancer cells and have shown promise in mice.

Jiang describes her project in this video, taken at NanoXpo 2018 this past May:



Poster title: "Cancer cell membrane-coated nanoparticles for anticancer vaccination"

NanoXpo is an annual event held by the Graduate Society of Nanoengineers to showcase graduate research in the UC San Diego Department of NanoEngineering.

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.

Engineers Think Business: von Liebig NSF I-Corps Program Launches 3rd Cohort

Mentors, entrepreneurs and students met in the Qualcomm Conference Room on Jan. 20, ready to dive in head first into Phase I of the 2015 National Science Foundation Innovation Corps program at UC San Diego hosted by the von Liebig Entrepreneurism Center.

The NSF I-Corps program aims to bridge the gap between business and technology through hand-on experiential classes designed for scientists and researchers and taught by experienced entrepreneurs.

The von Liebig Entrepreneurism Center became an I-Corps Site in 2013 and has already conducted two 10 week workshops. This quarter, the Center received 27 excellent applications and 13 teams have been accepted into the 6-week program that will prepare them for commercialization, while expanding their opportunities to receive funding for their technology. This is the third Phase I cohort of teams participating in the program bringing it to a total of 54. Teams that successfully complete the program are also eligible to compete for up to $50,000 and participate in the national NSF I-Corps program.

Nineteen mentors and 30 participants from various departments and schools including the Jacobs School of Engineering, Rady School of Management and Scripps Institute of Oceanography attended the program's first day of class. After the mentors introduced themselves with a brief background of their work and expertise, the students took center stage. Each team gave their 60 second pitch of the concept of their technology, the customer's problem they attempt to solve and the market they hope to reach.

Andrea Belz, PhD, MBA
(Photo by Anne Cusack, Los Angeles Times)

The program mentors and students then met Adrea Belz, Director of the Southern California I-Corps node, experienced angel investor, entrepreneur and business consultant for an invigorating presentation that encompassed how the program will challenge its students and what it takes to go from idea to a business. I-Corps Nodes and Sides are members of the National Innovation Network focused on bringing best practices and collaboration around technology commercialization in the country.

During her presentation, Belz urged students to step out of their comfort zones and get out of the building and talk to customers. With the help of Frank Chen, an MBA candidate from the Rady School of Management, Belz reenacted a customer interview demonstrating the importance in identifying your market and listening to customer needs.

“You’ve done the research and you’ve got the idea. Now, you won’t find answers in the classroom, and you won’t find them in the lab,” Belz said. “You’ll only find them out there.”

To practice, the teams and mentors broke into groups and conducted their own interviews, where each team asked questions to a mentor, who acted as the team's determined potential customer for their technology.

When class was called back into session, Belz encouraged the teams to iterate and pivot, to think with the business model, to turn guesses into facts and to fail before succeeding.

Throughout the evening, it was made clear that the I-Corps program will challenge students to think on their feet and interact with their market. The program will continue to meet weekly on Thursday evenings, from January 29 to March 12.

Student Team Practicing Customer Interviews

After three cohorts, teams that completed the two-phase program have drawn a lot of success. Some of the program's most recent successes include:

Nanolipo, led by a PhD student and professor in the Skaggs School of Pharmacy and the CACST-UCSD Center for Excellence in Nanomedicine, has designed a materila that improves liposuction procedures. In parallel with their scientific advancements, the team has begun incorporating the feedback of surgeons to their non-traditional approach, and have recently formed a company.

Plasmacaps, a team composed of a PhD student and processor in nanoengineering, has designed a powerful energy technology which improves energy density capacitors. In the I-Corps program, the team visited many customers and incorporated feedback into the compact, redesign of their nanocarbon energy capacitors. Plasmacaps was accepted into the accelerated National I-Corps Program in Washington D.C.

CocoonCam, led by a UC San Diego graduate student in Computer Science and Engineering, has designed a next-generation baby monitor that monitors the baby's health touch-free. In the I-Corps Program, he designed and conducted a series of interviews to obtain first-hand information validating CocoonCam's desirability to parents and institutions who will be utilizing it. They will soon begin product testing and are in a much stronger position to approach investors with the customer validation gleaned in I-Corps.

Eatsafe, led by a Biotechnology grad student at UC San Diego, has created a small portable device that can detect food pathogens by simply being in close proximity. Eatsafe team members took advantage of the I-Corps Program to interview several categories of customers for their device, determining that international travelers and people with food sensitivities would be the best early adopters. This, in turn, helped guide prototype development and marketing strategies for the device.