Mandi: Researchers at the Indian Institute of Technology Mandi have used natural polymer-based smart nanoparticles to treat colorectal cancer. These nanoparticles release the drug in response to stimuli that are specific to the cancer site only.

The findings of the research have been published in the Journal Carbhohydrate Polymers. The research has been led by Dr. Garima Agrawal, Assistant Professor, School of Basic Sciences, and co-authored by her students Dr. Ankur Sood and Ms. Aastha Gupta from IIT Mandi and Prof. Neal Silverman along with his team from the University of Massachusetts Medical School, Worcester, MA, United States of America. The research was funded by the Science and Engineering Research Board, Government of India along with IIT Mandi.

Colorectal cancer is a devastating disease leading to increased mortality worldwide and it also causes a heavy financial burden on the healthcare system globally. It is the third most common cancer in men and the second most common in women worldwide. It accounts for 8% of all cancer deaths making it the fourth most common cause of death due to cancer in the world.

Explaining the research, Dr. Garima Agrawal, said, “One of the driving interests among the material science and healthcare community performing interdisciplinary work is the development of biodegradable nanoparticles from renewable resources and designing them in such a way that they can release the drug in response to stimuli which are specific to cancer site only.”

Further, Dr. Agrawal, mentioned, “The designed system should be capable of supporting drugs having different solubility in water. In this regard, the simplest approach that we followed for developing biodegradable nanoparticles is using chitosan, which is a naturally derived polymer, in combination with disulfide chemistry.”

IIT Mandi researchers have developed redox-responsive chitosan/stearic acid nanoparticles (CSSA NPs) as drug carriers for both curcumin (hydrophobic; a component from turmeric that is used daily in food) and doxorubicin (hydrophilic) drugs delivery targeting colorectal cancer. This approach of combining anticancer drugs having a different mode of anticancer action allows to develop the systems for cancer therapy with enhanced efficacy.

Talking about the uniqueness of their research, Ms Aastha Gupta, research scholar, IIT Mandi, said, “We have synthesized nanoparticles based on disulfide (−S−S−) crosslinking chemistry via air oxidation of thiolated chitosan and thiolated stearic acid, thus avoiding the use of any external crosslinking agent. We have tried five different combinations of thiolated polymers to select the combination best suitable for obtaining stable and uniform nanoparticles. The presence of disulfide bonds allows the degradation of these smart nanoparticles at the tumour site owing to higher glutathione amounts in cancer cells.”

The researchers at IIT Mandi have developed biodegradable nanoparticles from renewable resources, thus reducing the dependency on petroleum-based polymers. These smart nanoparticles are stable under physiological conditions and degrade at tumor sites in the presence of redox stimuli of cancer cells. These nanoparticles can be used to successfully load and release both hydrophilic and hydrophobic drugs having a different anticancer mechanism which can help to improve the treatment efficiency.

Researchers have also investigated cancer cell killing efficiency through in vitro studies, and the colon targeting ability of the designed system through in vivo biodistribution experiments on c57bl/6j mice.

The research team further plans to perform biological studies to gain deeper insight into the potential of the developed system for colorectal cancer treatment.

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