Observed under an electron microscope, the biomimetic synthetic 24-mer ferritin nanoparticles resemble a delicate little flower. It's hard to imagine that its diameter is only 12 nanometers.
"This is a magical little molecule." Yan Xiyun, an academician of the Chinese Academy of Sciences and a researcher at the Institute of Biophysics of the Chinese Academy of Sciences, made no secret of her excitement and joy when talking about it.
In 2012, 2014 and 2016, the research group led by Yan Xiyun continuously published research results, which proved that this flower-like ferritin can not only diagnose tumors, but also effectively load chemotherapy drugs and accurately deliver them to tumor sites, thus realizing the integration of tumor diagnosis and treatment.
A New Drug: Ferritin Nanocarrier
In 2013, when interviewed by the media, Yan Xiyun summarized her dream as "One Kit, One Drug". Among them, the new drug refers to ferritin drug nanocarriers. Nowadays, ferritin nanoprobes and drug carriers are in the preclinical research stage.
The so-called ferritin is a kind of protein that has long been known. Previously, few people thought that it had other mysteries besides the function of storing iron. The new discovery and bionic transformation by Yan Xiyun's team made this humble protein "reborn".
The modified ferritin nanoparticles can be described as “similar in shape but not in essence” to natural proteins. According to Yan Xiyun, the shell of natural ferritin is a mixture of light and heavy chains; however, they found that only the heavy chain can recognize tumors. Thus, they created heavy-chain ferritin nanoparticles, enabling them to distinguish between normal cells and tumor cells. The cores of the ferritins were then replaced with magnetite and chemotherapy drugs, where the former can catalyze enzyme substrates to visualize tumor cells, while the latter allows for precise drug delivery to tumor sites to kill tumor cells.
“Only because we have accumulated prior knowledge can we cleverly combine the various physicochemical properties of ferritin to obtain this magical ‘magic particle,’” said Yan Xiyun.
The greatest magic of ferritin drug carriers lies in their ability to directly target tumors without the need to label any targeting molecules. This is because ferritin nanoparticles can bind to transferrin receptors on the tumor cell membrane, allowing for precise accumulation around tumor tissues. The carrier can release the drugs it carries only in the acidic microenvironment of the tumor. This high selectivity for tumor cells is something that other carriers lack, which is why ferritin drug carriers are most effective at killing tumors while avoiding damage to normal cells.
Moreover, ferritin drug carriers, as a type of natural protein, possess many advantages that inorganic nanomaterials cannot match. On one hand, they have good biocompatibility in the body and are less likely to cause immune rejection reactions; on the other hand, they automatically form through self-assembly, resulting in uniform particles with good reproducibility between batches, making them easy for clinical transformation. Additionally, the exceptional stability of ferritin significantly reduces production difficulty and costs.
The various exquisite and perfectly fitting characteristics make the ferritin nanocarrier seem like a gift from heaven. However, Yan Xiyun emphasizes that her discovery and recreation are inseparable from the years of research accumulation by her research team.
A New Kit: Nanoenzyme test strip
During an interview with a reporter from the “China Science Daily,” Yan Xiyun had just returned from the Women Scientists Conference organized by the Organization for Women in Science for the Developing World (OWSD). At the conference, she delivered a keynote presentation introducing a newly realized innovation: “nanoenzyme test strips.”
In 2014, West Africa experienced the most severe Ebola outbreak in history. Due to local conditions, testing technologies that require special instruments, laboratory facilities, and specialized personnel were difficult to popularize. Meanwhile, traditional test strips, which are economical and convenient, often lack sufficient sensitivity.
Thus, Yan Xiyun’s research team collaborated with Academician George Fu Gao from the Chinese Center for Disease Control and Prevention to replace the colloidal gold in traditional test strips with magnetic nanozymes, increasing the sensitivity by 100 times.
Magnetic nanozymes possess both magnetic properties for the separation and enrichment of samples, as well as catalytic activity that enables substrate color development. These dual characteristics make nanozyme test strips an ideal “platform technology.” By simply adding different probes, we can achieve various functions, making them applicable in fields such as medical diagnostics, forensics, customs, and livestock farming.
“Once I stepped down from the podium, I was surrounded by a group of female scientists,” Yan Xiyun said with a smile. Most of these scholars came from developing countries such as Kuwait and Nigeria. They are interested in this technology because, in countries and regions lacking instruments and equipment, small test strips are expected to become powerful tools for the rapid detection of viruses like Ebola and other epidemic pathogens.
At the end of 2015, the team led by Yan Xiyun won the Atlas Award with this technology, marking the first time Chinese scientists received this award. The award citation at that time was: “Research for a better world.”
“We cannot let down the award speech of Atlas; we must ensure that this scientific achievement serves the people and makes some contributions to the world,” said Yan Xiyun.
The “one kit,” which was initially a dream, is now becoming a reality. After many people read this paper, they have come from all over the world to discuss cooperation with Yan Xiyun. It is expected that next year, the nanoenzyme test kits will enter clinical application.
Two magic weapons: crossover and transformation
From “one drug” to “one kit,” the achievements have all extended from this prelude: the discovery of iron oxide nanoenzymes by Yan Xiyun’s research group in 2007. This achievement blurred the boundaries between inorganic materials and organic biology, promoting the integration of nanoscience and medicine.
After this, the team led by Yan Xiyun continued to study the catalytic mechanisms of nanoenzymes and expanded their applications, achieving many important technological advancements and gaining recognition from international peers. Recently, Springer Publishing invited her to write an English book titled “Nanoenzymes,” and the American Gordon Research Conferences invited her to organize a special session on nanoenzymes. “Our ability to embark on this interdisciplinary path is inseparable from the ‘very fertile soil’ provided by the Institute of Biophysics,” she said.
In 2003, the Key Laboratory of Interdisciplinary Research at the Institute of Biophysics was established, bringing together a group of talents from various disciplines such as physics, chemistry, and materials science. Every Friday, the Laboratory provides tea and coffee, allowing these scholars to sit together and chat casually.
At first, everyone had little common language. However, through constant exposure and observation, Yan Xiyun gradually understood the needs and focal points of different disciplines, attempting to integrate perspectives from biology. It was this collision of ideas that provided her with the opportunity to consider how to address biological problems from the perspective of nanoscience.
Starting from collaboration with other disciplines, Yan Xiyun’s team has broadened its path of cooperation and is currently working with clinical doctors and enterprises. She stated that she is willing to transfer maximum benefits to her collaborators. In this way, her research results can step out of the laboratory and realize their maximum value.
“The significance of what we do is to bridge the communication gap between research institutions and enterprises, helping original ideas from Chinese people take root and flourish. We want these research achievements to become a blessing for society, allowing our independently developed ‘nano flowers’ to bear abundant fruits,” said Yan Xiyun.
(Originally published in “China Science Daily” on May 30, 2016, Page 2, "Science and Technology Conference")
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