Rice University scientists Jeffrey Hartgerink, Brett Pogostin and Kevin McHugh have developed SABER, a peptide hydrogel system for drug delivery. Photos courtesy Rice University.

A team of Rice University scientists has developed a new drug delivery platform that researchers say can slow the rate of drug release, which has major implications for drug efficacy and potentially cancer immunotherapy.

The research was published in Nature Nanotechnology, and supported by the National Science Foundation, the National Institutes of Health, the Cancer Prevention and Research Institute of Texas and the Welch Foundation.

In the study, the team demonstrated how a peptide hydrogel functions as a three-dimensional network that controls the rate of release across a range of medication types, including small-molecule drugs and biologics such as insulin and antibodies. The system, called self-assembling boronate ester release (SABER), uses reversible chemical bonds between the peptide and the drug molecule to extend the duration of drug release. Instead of passing quickly through the net, the drug gets temporarily “stuck” each time it binds to the peptide, which slows its passage out of the hydrogel, according to Rice.

The researchers formulated a tuberculosis-treating drug into a hydrogel. They used it to treat infected mice with a single injection of the drug-laden hydrogel. In the test, the hydrogel outperformed almost daily oral administration of the medication over two weeks. Insulin packaged in SABER hydrogels successfully controlled blood sugar levels in diabetic mice for six days in another set of experiments.

Brett Pogostin, a Rice doctoral alum who led the development of SABER and served as first author of the study, began working on self-assembling peptides as an undergraduate student at Rice. Jeffrey Hartgerink, a professor of chemistry and bioengineering at Rice, and Kevin McHugh, associate professor of bioengineering and chemistry and a Cancer Prevention and Research Institute of Texas scholar, advised Pogostin and served as corresponding authors on the study.

Pogostin’s work aimed to bridge foundational materials research and biomedical applications. SABER was inspired by a drug delivery course taught by McHugh, where Pogostin learned about dynamic covalent bonds used in glucose sensing, where the bonds reversibly form and break apart. That quality inspired Pogostin to adapt the concept for drug delivery.

“Brett really drove this project in a way that is, in my experience, unusual for a graduate student,” Hartgerink said in the news release. “It’s a very versatile approach. You can make both small-molecule drugs and very large biologics sticky with the type of chemistry that Brett developed.”

The team demonstrated the platform in two different use cases with Tuberculosis and Type 1 diabetes, with SABER simplifying dosing and enhancing the efficacy of the drugs. Hartgerink described the current SABER system as “generation one,” and plans to work to make it widely applicable. He is looking into how SABER could be applied to cancer immunotherapy.

“What I’m really passionate about right now is cancer prevention — trying to think about how we can use materials to prime the immune system to prevent cancer from ever happening as opposed to just treating it,” Pogostin added.

Rice and MD Anderson scientists are researching new methods for treating brain cancer by overcoming the blood-brain barrier. Photo via Getty Images.

Rice, MD Anderson receive $1.5 million to further brain cancer research

fresh funding

Rice University chemist Han Xiao, who also serves as director of the university’s Synthesis X Center, and cancer biologist Dihua Yu of The University of Texas MD Anderson Cancer Center have received a three-year, $1.5 million grant from the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation.

The funding will allow them to continue their research on treating brain metastasis by overcoming the blood-brain barrier, or the BBB, according to a news release.

Brain metastasis is the leading form of brain cancer, with survival rates below 20 percent within a year of diagnosis, according to the National Library of Medicine. It commonly originates from breast, lung and melanoma cancers.

The BBB typically acts as a protective barrier for the brain. However, it prevents most drugs from being able to directly reach the brain. According to Rice, only 2 percent of FDA-approved small molecule drugs can penetrate the BBB, limiting treatment options.

Xiao and Yu’s approach to dealing with the BBB includes a light-induced brain delivery (LIBD) platform. The advanced system employs nanoparticles that are embedded with a near-infrared dye for the transport of therapeutic agents across the BBB. The research will evaluate the LIBD’s ability to improve the delivery of small-molecule drugs and biological therapies. Some therapies have shown potential for reducing cancer growth in laboratory studies, but they have struggled due to limited BBB penetration in animal models.

“Our LIBD platform represents a novel strategy for delivering drugs to the brain with precision and efficiency,” Xiao said in a news release. “This technology could not only improve outcomes for brain metastasis patients but also pave the way for treating other neurological diseases.”

The Kleberg Foundation looks for groundbreaking medical research proposals from leading institutions that focus on “innovative basic and applied biological research that advances scientific knowledge and human health” according to the foundation.

“This research is a testament to the power of collaboration and innovation,” Xiao said in a news release. “Together, we’re pushing the boundaries of what’s possible in treating brain metastasis and beyond.”

Rice launched the Synthesis X Center, or Synth X, last spring. It was born out of what started about eight years ago as informal meetings between Xiao's research group and others from the Baylor College of Medicine’s Dan L Duncan Comprehensive Cancer Center. It aims to turn fundamental research into clinical applications through collaboration.

“This collaboration builds on the strengths of both research teams,” Xiao said in the release. “By combining SynthX Center's expertise in chemistry with Dr. Yu's expertise in cancer biology and brain metastases, we aim to create a transformative solution.”

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Houston doctor wins NIH grant to test virtual reality for ICU delirium

Virtual healing

Think of it like a reverse version of The Matrix. A person wakes up in a hospital bed and gets plugged into a virtual reality game world in order to heal.

While it may sound far-fetched, Dr. Hina Faisal, a Houston Methodist critical care specialist in the Department of Surgery, was recently awarded a $242,000 grant from the National Institute of Health to test the effects of VR games on patients coming out of major surgery in the intensive care unit (ICU).

The five-year study will focus on older patients using mental stimulation techniques to reduce incidences of delirium. The award comes courtesy of the National Institute on Aging K76 Paul B. Beeson Emerging Leaders Career Development Award in Aging.

“As the population of older adults continues to grow, the need for effective, scalable interventions to prevent postoperative complications like delirium is more important than ever,” Faisal said in a news release.

ICU delirium is a serious condition that can lead to major complications and even death. Roughly 87 percent of patients who undergo major surgery involving intubation will experience some form of delirium coming out of anesthesia. Causes can range from infection to drug reactions. While many cases are mild, prolonged ICU delirium may prevent a patient from following medical advice or even cause them to hurt themselves.

Using VR games to treat delirium is a rapidly emerging and exciting branch of medicine. Studies show that VR games can help promote mental activity, memory and cognitive function. However, the full benefits are currently unknown as studies have been hampered by small patient populations.

Faisal believes that half of all ICU delirium cases are preventable through VR treatment. Currently, a general lack of knowledge and resources has been holding back the advancement of the treatment.

Hopefully, the work of Faisal in one of the busiest medical cities in the world can alleviate that problem as she spends the next half-decade plugging patients into games to aid in their healing.

Houston scientists develop breakthrough AI-driven process to design, decode genetic circuits

biotech breakthrough

Researchers at Rice University have developed an innovative process that uses artificial intelligence to better understand complex genetic circuits.

A study, published in the journal Nature, shows how the new technique, known as “Combining Long- and Short-range Sequencing to Investigate Genetic Complexity,” or CLASSIC, can generate and test millions of DNA designs at the same time, which, according to Rice.

The work was led by Rice’s Caleb Bashor, deputy director for the Rice Synthetic Biology Institute and member of the Ken Kennedy Institute. Bashor has been working with Kshitij Rai and Ronan O’Connell, co-first authors on the study, on the CLASSIC for over four years, according to a news release.

“Our work is the first demonstration that you can use AI for designing these circuits,” Bashor said in the release.

Genetic circuits program cells to perform specific functions. Finding the circuit that matches a desired function or performance "can be like looking for a needle in a haystack," Bashor explained. This work looked to find a solution to this long-standing challenge in synthetic biology.

First, the team developed a library of proof-of-concept genetic circuits. It then pooled the circuits and inserted them into human cells. Next, they used long-read and short-read DNA sequencing to create "a master map" that linked each circuit to how it performed.

The data was then used to train AI and machine learning models to analyze circuits and make accurate predictions for how untested circuits might perform.

“We end up with measurements for a lot of the possible designs but not all of them, and that is where building the (machine learning) model comes in,” O’Connell explained in the release. “We use the data to train a model that can understand this landscape and predict things we were not able to generate data on.”

Ultimately, the researchers believe the circuit characterization and AI-driven understanding can speed up synthetic biology, lead to faster development of biotechnology and potentially support more cell-based therapy breakthroughs by shedding new light on how gene circuits behave, according to Rice.

“We think AI/ML-driven design is the future of synthetic biology,” Bashor added in the release. “As we collect more data using CLASSIC, we can train more complex models to make predictions for how to design even more sophisticated and useful cellular biotechnology.”

The team at Rice also worked with Pankaj Mehta’s group in the department of physics at Boston University and Todd Treangen’s group in Rice’s computer science department. Research was supported by the National Institutes of Health, Office of Naval Research, the Robert J. Kleberg Jr. and Helen C. Kleberg Foundation, the American Heart Association, National Library of Medicine, the National Science Foundation, Rice’s Ken Kennedy Institute and the Rice Institute of Synthetic Biology.

James Collins, a biomedical engineer at MIT who helped establish synthetic biology as a field, added that CLASSIC is a new, defining milestone.

“Twenty-five years ago, those early circuits showed that we could program living cells, but they were built one at a time, each requiring months of tuning,” said Collins, who was one of the inventors of the toggle switch. “Bashor and colleagues have now delivered a transformative leap: CLASSIC brings high-throughput engineering to gene circuit design, allowing exploration of combinatorial spaces that were previously out of reach. Their platform doesn’t just accelerate the design-build-test-learn cycle; it redefines its scale, marking a new era of data-driven synthetic biology.”