The discovery of a novel nanosystem that makes cancer cells more susceptible to chemotherapy treatments

Work done in the lab of Prof. Santosh Kumar Misra at the Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur

About author

Aishwarya received her B.Tech. in biotechnology at VIT Vellore, where she participated in numerous course-embedded projects in nanotechnology, antimicrobial resistance, food technology, etc., exposing her to the vast scope of biotechnology in all aspects of life. Later, as an M.Tech. student in Prof. Misra’s lab in the Biological Science and Bioengineering department at IIT Kanpur, she studied cancer-associated microbiomes, biosensors for disease detection, and nanoscale carbon-based strategies for biomedical applications. The current publication is based on one possible use of an iron-based nanoscale carbon product that she worked on for her master’s thesis.

Interview

How would you explain your research outcomes to the non-scientific community?

According to Dr Siddhartha Mukherjee’s book on cancer, as a species, if we are the ultimate product of Darwinism, so is this disease that lurks within us. At their innate core, cancer cells are hyperactive, survival-endowed, scrappy, fecund, inventive copies of ourselves. When you try to kill cancer cells with medicines it either throws them out or decapacitates them.

We investigated what prevents these cancer cells from dying and observed that it increases the levels of glutathione, a well-known antioxidant that protects against oxidative stress and even aids in drug expulsion from cells. To prevent the guardian glutathione molecules from aiding cancer cells in their survival against used medications, we explored what could be used as a bait. We found iron ions to be one such option.

Delivering free iron ions will neither ensure that it reaches the target site nor will be safe for non-cancer cells, resulting in iron toxicity. To carry and deliver iron ions to the glutathione molecules in cancer cells, we created a biocompatible (does not affect neighbouring healthy cells) and fluorescent nanosystem (can be tracked while it accumulates at the cancer site). Cancer medications can operate considerably more efficiently and kill cancer cells with significantly lower doses (in our case,>6-fold lower) than before, while glutathione molecules are engaged in binding to iron ions, here supplied by our nanosystem. Such a lower dosage is expected to alleviate side effects on non-cancer cells.

How do these findings contribute to your research area?

We hope our work will incite other researchers to explore the role of glutathione depletion in improving chemotherapy efficacy, such that the dreaded side effects can be minimised. Further, in the field of nanoscale carbon materials, this novel biocompatible product is envisaged to be used as a multifunctional candidate that can be improvised for specific applications. We envision that it will promote the investigation of nanoscale materials beyond their classic role as trojan horses, i.e., drug delivery carriers.

“Work will incite other researchers to explore the role of glutathione depletion in improving chemotherapy efficacy, such that the dreaded side effects can be minimised.”

What was the exciting moment during your research?

During my master’s degree, I began with a project that included microbiology techniques and approaches that I was familiar with, but due to COVID’19, I ended up working in this project from a new field, involving techniques that I had not used before. I must have redone even the most basic experiment and data analysis dozens of times before presenting it to my PI. It was a novel system with few indirect references in the literature, and every experiment was exciting since we were not restricted to what to expect. After analysing its features, we began to investigate prospective applications. It was a true learning experience that taught me how to choose which questions to ask.

A mother can still anticipate what to see on the ultrasound screen, but I had no idea of the nanosystem’s morphology. Thus, I would say the day I viewed the iron-nanosystem using TEM for the first time was the most exciting and memorable moment.

What do you hope to do next?

Based on the data we have, this nanosystem and its precursors can be studied from a variety of perspectives, and we have other potential applications in mind such as glutathione level detection in body fluids and biopsy samples, targeted therapy, image-guided surgery, and so on all of which are thoroughly discussed in the paper. Thus, evaluating all these aspects is in the pipeline. While working in Dr. Misra’s lab, I was surprised by the vast array of uses for just nanoscale carbon materials in biological research. I plan to continue my study in this exciting field by pursuing a PhD in nanomedicine and contributing to the alleviation of the growing burden of debilitating diseases by developing cost-effective nanotechnology-based strategies.

Where do you seek scientific inspiration from?

Dr. APJ Abdul Kalam has had a profound influence on me in terms of perseverance in scientific research in the face of adversity. Apart from him, fabric merchant turned microbiologist Antonie Van Leeuwenhoek motivates me to believe that one can make astounding contributions to science by simply being curious enough.

How do you intend to help Indian science improve?

My batchmates either left science due to a lack of sufficient exposure (resulting in a lack of confidence and desire) or, despite having the skills and enthusiasm in the field, shifted to the IT sector in order to have the time and resources to support their families. I also witnessed others quitting the field during or after their master’s due to the underlying pressure.

We all know that it is not as financially rewarding as other sectors and that it requires so much more time and energy that one must put everything else on hold. I’ve realised that the 3Fs; funds (to facilitate faster research), flexibility (in age limits, working hours, fund utilisation), and friendship (support for students and young faculty, collaboration among labs and institutes) are critical aspects that we still lack. Thus, I intend to advocate for and promote these aspects and contribute my part to making the research environment in India more conducive. In addition, I intend to acquaint high school and undergraduate students with research methodologies and the newest technology via videos and MOOCs (massive open online courses) and eventually contribute to the development of interactive virtual labs.

Reference

Naik, Aishwarya, Krishan Kumar, Niranjan Chatterjee, and Santosh K. Misra. “Polyphenol-Based Nanoscale Iron Exchangers for Regulating Anticancer Chemotherapy by Modulating the Activity of Intracellular Glutathione.” ACS Applied Bio Materials (2022). https://pubs.acs.org/doi/10.1021/acsabm.2c00887

Copy Editor

Sukanya Madhwal

Ph.D. student at inStem Bangalore

Sukanya hails from a small town, kotdwara in Uttarakhand. She completed her Masters’ degree in Biotechnology from Banasthali Vidyapith, Rajasthan. After this, she served as a graduate teacher for one year at P.G. College, Kotdwara, Uttarakhand. In 2014, she qualified for the JGEEBILS exam conducted by NCBS/TIFR and joined as a Research Scholar (Ph.D. student) in Dr. Tina Mukherjee’s lab at inStem. Currently, she continued working as a bridging post-doc in Dr. Tina Mukherjee’s lab. Besides work, she loves reading non-fiction books, enjoys gardening, and cooking delicious food.

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