Kattesh Katti remembers the warm summer evening in India when his life was forever changed. It was a spectacular ending to a day spent out on the cricket fields at the local university. Katti and his friends were following a shortcut home when the boys saw something peculiar. Test tubes, bottles, and beakers, abandoned by the university’s chemistry department for one reason or another, sat under the shade of a tree. Fascinated, Katti collected an assortment of containers and brought them home.
Over the next few years, Katti would run experiments out on his balcony, trapping sulfur fumes and mixing them with water. Two of his cousins, studying science and math, encouraged his interests, quizzing him and inviting him to tour their respective universities.
Now, far from the cricket fields, Katti continues to do research involving unusual, even humble, substances. As the director of the University of Missouri’s Cancer Nanotechnology Platform, Katti focuses on alternative cancer treatments using minuscule particles, called nanoparticles, that can be treated with radiation to fight tumors. Katti has found ways to use natural compounds found in cinnamon, tea leaves, soybeans and other plants to produce and deploy these nanoparticles with fewer toxic byproducts.
Katti’s work in this field led Nobel Prize winner Norman Borlaug to call him the “Father of Green Nanotechnology.” He has received national and international awards for his work and has been elected as a fellow by the American Association for the Advancement of Science. In 2015 he was elected as a fellow of the National Academy of Inventors.
“I don’t work for recognition. Whatever has happened is [because of] collaboration,” Katti said. “I’m not someone who needs recognition all the time, or anytime, for that matter.”
Katti and his siblings born to a low-income family in India were often forced to choose between eating lunch and dinner. Despite this, his parents consistently emphasized the importance of education and encouraged him to continue learning.
He began his education in organic chemistry and entered a Ph.D. program at the Indian Institute of Science. In February of 1985, Katti was selected into the Alexander von Humboldt Fellowship program in Germany. Two years later he took a research position in Canada, where he worked for two and a half years.
In 1990, he accepted a position at MU to research the use of metals in medicine. During his studies he realized that the metal particles he was injecting into the mice needed to be smaller in order to work efficiently; his training in physics and chemistry allowed him to venture into nanotechnology.
“Nanotechnology is a disruptive science because it breaks the boundaries between different disciplines,” Katti said.
In his more recent research, Katti is working to develop “green” cancer therapies that use natural spices and plants to help target cancer cells.
Conventional cancer treatment causes a lot of collateral damage. Chemotherapy may kill cancer, but it also kills normal, healthy cells, like those in bone marrow, the digestive tract, and hair follicles. The chemicals can also collect in the liver and kidneys.
“Chemotherapy is pretty toxic,” said Wynn A. Volkert, a former professor of radiology at MU. “You are targeting a lot of cells, healthy ones.”
With targeted nanoparticles, Volkert said, “you hope that this particular way is only targeting the cancer cells.”
How it works
It works like this: First Katti treats nanoparticles with radiation, which enables them to emit beta rays that destroy cancer cells on contact.
During the radiation process only some of the gold nanoparticles become radioactive, while others do not. Both the radioactive and non-radioactive nanoparticles have therapeutic effects. While the radioactive nanoparticles destroy the cancer cell, the non-radioactive nanoparticles suppress the cells’ growth.
Next, each nanoparticle is enveloped in layers of plant-based chemicals called phytochemicals. Katti uses phytochemicals found in cinnamon, tea leaves, and other plants and spices that have an affinity for particular proteins expressed by the cancer cells.
The phytochemicals act as a navigator, directing the nanoparticle to the cancer cell, where the phytochemicals bind to the cancer cell’s protein receptor sites. Much like a Trojan horse, the phytochemicals disguise the rest of the nanoparticle, tricking the cancer cell into opening its gates. Once inside the cancer cell, the radioactive nanoparticle emits beta particles that destroy the cell.
In the case of metastasis, when cancer cells travel throughout the body, the phytochemicals go on a high-speed chase to bring the nanoparticles directly to the cancer cells before they develop into a tumor.
As with any type of radiation therapy, there is some risk of radiation toxicity. However, studies so far in mice and dogs have indicated the radiation is optimally applied to the cancer cells, making the outlook for human treatment an optimistic one. Katti and his team have more dog studies to complete before applying for human administration.
Katti and his team are also exploring other natural compounds to treat cancer. Melissa Zaidi, one of Katti’s interns from France, is working towards a master’s in nanotechnology. In the lab she is using chitosan, a compound found in the shells of crustaceans, to synthesize gold nanoparticles. Chitosan has been used in medicinal studies, as it is biodegradable and has some anti-bacterial properties, Zaidi said. Because the chitosan has a positive charge, it is attracted to the negative charge in cancer cell membranes.
“There are probably other influences, but so far we have not understood how it really works,” Zaidi said. “It would be really great to find the mechanism that makes it work.”
How it started
The genesis for Katti’s cancer treatment using gold compounds began with his collaborative efforts with oncologist Hideo Kamei, whom he had met at a conference in Japan in 1995. At the time, Katti had been using the gold compounds as models for producing radioactive gold compounds. The purpose was to apply the radioactive gold compounds in cancer therapy. Following Katti’s presentation, Kamei approached him to try the non-radioactive models for cancer therapy application instead.
Their collaborative efforts made its way back to MU when Carolyn Henry, an oncology professor in the Department of Veterinary Medicine and Surgery, discussed using the gold compounds Katti had created to treat non-Hodgkin’s lymphoma in dogs, which mimics the same disease in humans. The result of the study were a couple of canines that no longer had non-Hodgkin’s lymphoma.
The original procedure Katti used to create the gold nanoparticles required the use of hazardous chemicals, such as sodium borohydride and hydrazine. Katti resolved this problem by substituting plants. Plants like cinnamon and tea leaves, which are staples in the human diet, contain electron-rich antioxidants necessary for converting the base of the nanoparticles, gold compounds, into the gold nanoparticles. The antioxidants reduce the gold compounds down to the nanoparticles through chemical reduction and then stabilize them to prevent them from binding together.
Since then he has continued to study alternative plants able to create nanoparticles from gold compounds. He hopes his simple method of developing gold nanoparticles using few ingredients has opened a new door for developing countries. Farmers who produce crops could potentially have a new avenue in their respective markets by taking advantage of opportunities in gold nanoparticle research, which could boost the agricultural economy, Katti said. The research industry can also blossom with this technology without causing any environmental damage, Katti said.
“Even though it was a small discovery, its implications are enormous,” Katti said.
Where to now?
Katti strives to build relationships with potential collaborators in order to advance his research. He wants to make sure his work further develops through different people.
“Meeting and collaborating with scientists of interdisciplinary origin and working under a whole different set of facilities and environments is a recipe for breeding new scientific ideas,” Katti said. “There is only so much you can engage in collaborations within the campus.”
Volkert, who convinced Katti to come to MU, noted Katti’s affinity for working with researchers around the world. Already, Katti has partnerships with a university in South Africa and is working to expand partnerships into Europe and Asia.
“I think of [him as] someone who is innovative and willing to go the extra mile to establish new relationships,” Volkert said. “He’s been a really good ambassador for the university.”
Building collaborative relationships takes time. Add that on top of the work Katti is completing at home and in the lab, it can eventually take their toll. Katti is an early riser, using the hours between 3 a.m. and 7 a.m. to breeze through the work he completes at home before heading off to the lab.
“I tell him he should reduce his workload and relax a little bit more,” his wife, Kavita said. “[But] he is very passionate about his work.”