At the heart of Zhang’s research lies a deceptively simple idea: rather than trying to engineer, molecule by molecule, a synthetic particle capable of navigating the treacherous terrain of the human bloodstream, why not simply borrow the camouflage that nature has already perfected? His laboratory takes membranes harvested from human cells and wraps them around biodegradable nanoparticles roughly one-thousandth the width of a human hair. Once cloaked, these particles inherit some of the biological powers of the cells they mimic. Red blood cell membranes allow the particles to circulate undetected for extended periods, delivering drugs to the tissues that need them. White blood cell membranes endow the particles with an entirely different talent: the ability to soak up and neutralize the toxic molecules that drive sepsis, to attack infection-causing fungi, and even to intercept the inflammatory signals that fuel rheumatoid arthritis.

The insight emerged from a longstanding frustration in nanomedicine. Nanoparticles can carry enormous payloads of medicine relative to their size, but once injected into the bloodstream they run headlong into the immune system, a surveillance network exquisitely designed to eliminate anything that does not belong. Researchers had long tried to make synthetic particles less conspicuous, coating them with polymers and other materials intended to suppress immune recognition, with limited success. Zhang’s alternative was more radical and, in retrospect, more elegant. Instead of making synthetic particles harder to recognize, he would make them genuinely recognizable as self. His team began with red blood cells, collecting their membranes and wrapping them around nanoparticles while carefully preserving the proteins, lipids, and carbohydrates that naturally stud the cell surface.

The landmark demonstration came in 2011, when Zhang’s group published a paper in the Proceedings of the National Academy of Sciences showing that membrane-coated nanoparticles could circulate in the bloodstream for up to two days, far longer than many conventional nanoparticles of the era. Zhang has often described the strategy as an engineering shortcut. Recreating the staggering molecular complexity of a cell surface from scratch, with its precisely organized arrays of proteins, lipids, and carbohydrates, would be a monumental synthetic challenge. Using the membrane itself sidesteps that problem entirely. The beauty of the technology, as Zhang puts it, is that the complexity does not have to be rebuilt; it can simply be transferred intact onto the surface of a particle small enough to travel wherever the blood goes.

The disguise offered far more than extended circulation time. Red blood cells are natural targets for bacterial toxins that kill cells by punching holes in their membranes, and particles dressed as red blood cells proved irresistible to those toxins. Zhang’s team christened these decoys nanosponges for their ability to soak up toxins and divert them away from real cells. The approach showed promise against toxins produced by dangerous bacteria, including methicillin-resistant Staphylococcus aureus, better known as MRSA. By removing toxins from circulation, the nanosponges helped weaken MRSA infections, and because the strategy does not depend on antibiotics at all, it points toward a way of treating drug-resistant infections without fueling the resistance crisis that has rendered so many conventional drugs ineffective.

From that first success, Zhang began borrowing membranes from an expanding cast of cell types. His laboratory developed macrophage-coated nanosponges to capture the toxins and inflammatory molecules involved in sepsis, the uncontrolled immune response triggered by bacterial infection that can cascade into organ damage and death. Because macrophage membranes carry receptors for a broad spectrum of sepsis-causing molecules, the particles function as universal traps rather than single-target drugs, an approach Zhang argues is more effective than attacking one disease-causing molecule at a time. Neutrophil-coated nanosponges followed, designed to treat rheumatoid arthritis. Neutrophils are immune cells that rush to sites of inflammation, where they can perpetuate a chain reaction of tissue damage; the neutrophil nanosponges acted as decoys, intercepting inflammation-causing molecules before they could keep the destructive cycle turning.

More recently, the concept has been extended to drug-resistant fungal infections caused by Candida albicans, the organism behind common yeast infections and, in severe cases, deadly bloodstream infections. Since macrophages naturally recognize Candida, Zhang’s researchers used macrophage membranes to build nanoparticles that could seek out fungal cells. In experiments, the particles attached to Candida cells, physically damaged them, and helped stimulate the body’s own immune defenses. The same membrane-borrowing principle has also produced platelet-coated nanoparticles for targeted drug delivery. Platelets, the tiny cell fragments that bind to damaged blood vessels to stop bleeding, also preferentially bind to certain pathogens, including MRSA. When loaded with medicine, the platelet-disguised particles delivered their cargo directly to damaged arteries and bacterial infections, healing them with only a fraction of the typical dose while minimizing side effects elsewhere in the body.

For Zhang, the urgency of translating laboratory discoveries into real medicine has a deeply personal origin. When he joined UC San Diego in 2008, his laboratory was housed in the Moores Cancer Center, where he watched dozens of cancer patients pass through the building every day. That environment, he has said, provided a natural intersection between engineering and medicine, and seeing so many people suffering left him feeling a scientist’s responsibility to do something that could make a difference. His path to that mission was unconventional. As an undergraduate studying chemical engineering at Tsinghua University in Beijing, he helped develop an unusually tough plastic and could have commercialized it and opened a factory. Instead he left for a Ph.D. in chemical engineering at the University of Illinois at Urbana-Champaign and a postdoctoral fellowship at MIT. Though the plastics factory never materialized, his entrepreneurial instincts did: he co-founded biotech startups, including San Diego-based Cellics Therapeutics, which is working to move the red blood cell and macrophage nanosponges toward clinical studies for bacterial infections, autoimmune diseases, and inflammatory diseases, while also exploring cellular nanoparticles that could neutralize a wide variety of pathogens, including bacterial toxins and viruses.

That commitment to scalability now shapes his leadership as chair of his department, where he has worked to bridge the traditionally separate territories of chemical engineering and nano engineering. Nano engineering, as Zhang explains it, centers on innovative nanoscience and technologies operating at very small scales, while chemical engineering focuses on large-scale production, manufacturing, and the processes that turn materials into products. His effort to fuse the two was recognized with a $21 million gift to the department in 2024 from San Diego business leader and philanthropist Aiiso Yufeng Li and his family, and the merged department now operates under the slogan Scalable Innovation, allowing undergraduates to move seamlessly between nanoscale science and the realities of manufacturing at scale. Zhang’s career has accumulated a long list of distinctions along the way: election as a fellow of the National Academy of Inventors in 2020, the American Association for the Advancement of Science in 2018, and the American Institute for Medical and Biological Engineering in 2015, plus recognition on Popular Science’s Brilliant 10 list in 2016, MIT Technology Review’s top 35 young innovators in 2013, and repeated appearances among Clarivate’s Most Highly Cited Researchers.

The reach of Zhang’s idea now extends well beyond his own laboratory. In the past decade, more than 10,000 papers on cell membrane coating technology have been published by hundreds of laboratories worldwide, a testament to how thoroughly the approach has permeated the field. Zhang notes that laboratories around the globe are using the technology to advance their own research, an impact that reaches researchers he may never meet. At UC San Diego, he joins a select company of MacArthur Fellows on the current faculty, including computer science and engineering professor Stefan Savage, Division of Social Sciences Dean Carol Padden, anthropology professor Guillermo Algaze, and philosophy professor Nancy Cartwright, along with several emeritus recipients. Chancellor Pradeep K. Khosla congratulated Zhang on what he called a tremendous, well-deserved honor, crediting the professor with turning cellular membranes into a platform technology to deliver medicines and combat infectious disease and inflammation. As the fellowship’s unrestricted funds free him to pursue whatever directions he chooses, the cellular disguises that began as an engineering shortcut now stand as one of the most influential ideas in modern nanomedicine, with the potential to redefine treatment for cancer, infection, and inflammatory disease alike.

Subject of Research: Cell-mimicking nanoparticles for drug delivery and treatment of infectious and inflammatory diseases

Article Title: Nanomedicine pioneer at UC San Diego awarded MacArthur ‘Genius Grant’

Article References: Nanomedicine pioneer at UC San Diego awarded MacArthur ‘Genius Grant’. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: MacArthur Fellowship, nanomedicine, cell membrane-coated nanoparticles, drug delivery, nanosponges, antibiotic resistance, sepsis, rheumatoid arthritis, MRSA, Candida albicans, UC San Diego, biotechnology