breast cancer

Aurora A Kinase

enzyme

glucose

Six years ago, Kathryn Takamura, a research student from The Ohio State University, visiting the Indian Institute of Science Education and Research (IISER) in the city, set the ball rolling for a significant study on a drug carrier to isolate and killcells. Takamura, a student of biochemistry, initiated a dialogue between both the biology and chemistry departments of IISER, Pune.The starting point for the project was to stop the growth of, anthat is associated with the occurrence of cancer. “Aurora Kinase A was the molecule that we originally envisaged targeting. Along the way, we realised that different cancers take up this nanovesicle differently. Among the cancers that took it up well, the one where Aurora Kinase is active and could hence be targeted turned out to be breast cancer cells,” says Dr Nagaraj Balasubramanian, cell biologist and associate professor, biology department at IISER Pune.In a first, the challenges of poor drug solubility and transport across cell membranes for the drug Alisertib, also known as MLN8237, have been overcome with this polymer nanovesicle.The nanovesicle is shaped like a ball and the drug is stored in its outer membrane. Several nanosystems and different drugs were tested in the lab, adds Dr M Jayakannan, professor and chair, chemistry department, IISER, Pune. “Only this particular nanovesicle was able to take this drug,” he adds, referring to MLN8237, a drug known to inhibit growth of aurora kinases. Professor Jayakannan’s team, including research student Nilesh Deshpande, designed the multi-drug carrying, self-assembling nanovesicle made from multiplemolecules or dextran polysaccharides, which are linked using a derivative from cashew nut extract. “We used a plant-based derivative to modify dextran and make the nanovesicle, so that when it disintergrates in the body, it is completely natural and should be non-toxic to living cells and it is,” says Dr Jayakannan. The study has been conducted on cultured cells inside a lab and it is too early to determine what stage of cancer the drug could be administered.Animal testing will be the next step for the study, which was published in the American Chemical Society, a leading scientific journal.The study could not have been such asuccess if it had not been for the collaboration, stresses Dr Jayakanna, who has been working on natural polymers and nanovesicles since 2010. “It has allowed us to think differently about drug chemistry. We are now able to ask questions like, what the delivery mechanism for drug is and how stable is it. Based on the confidence that we could collaborate on this study, we feel we will be able to work on new problems together as well. Such a collaboration also works for students,” says Dr Balasubramanian. Deshpande for instance learnt tissue culture from Siddhi Inchanalkar, graduate student of the Biology department, studying adhesion-mediated regulation of aurora kinase and its role in cancers. Adds Dr Jayakannan, “It has helped us take this problem and address it at a different level. I have come to believe that after a certain point, it is impossible to solve some problems without this kind of collaboration.”