IIT Gandhinagar Researchers Develop DNA-based Nanostructure for Targeted Cancer Therapy
Study demonstrates the use of Vitamin E-derived molecule to enhance the nanostructure’s interaction with cancer cells
Gandhinagar: Conventional cancer treatments, such as chemotherapy, often lack specificity and can damage both cancerous and healthy cells, leading to severe side effects. With this in mind, researchers at Indian Institute of Technology Gandhinagar (IITGN) have developed DNA nanostructures called tetrahedrons and modified them by attaching a Vitamin E-derived molecule called alpha-tocopherol succinate (αT), which can disrupt vital functions inside cancer cells while acting protectively in healthy cells. By incorporating αT into the DNA tetrahedrons, the researchers significantly enhanced cellular uptake and improved anticancer efficacy, resulting in more selective and effective elimination of cancer cells.
At the heart of this study is the promising approach of DNA nanotechnology, which involves engineering DNA into highly controlled nanoscale structures capable of carrying drugs, imaging agents or therapeutic molecules. By exploiting the programmable self-assembly of DNA, researchers can construct nanoscale architectures with well-defined size, shape and functionality. Among these nanostructures, DNA tetrahedrons have gained considerable attention as drug delivery platforms due to their structural stability, biocompatibility, low immunogenicity, and ease of functionalisation. However, despite these advantages, researchers often find that their therapeutic potential is limited by relatively inefficient cellular internalisation and restricted intracellular delivery.
Addressing these limitations, the findings of the study were published in ACS Applied Bio Materials in the paper titled, “Alpha-Tocopherol-Conjugated DNA Tetrahedron with Enhanced Cellular Uptake and Cytotoxicity for Cancer Therapeutics”. Explaining the broader significance of the work, the corresponding author Prof Dhiraj Bhatia, Associate Professor at IITGN’s Department of Biological Sciences and Engineering said, “What makes this work exciting is that we are starting to see how intentional molecular design can influence biological behaviour in a very controlled way. Even subtle changes at the surface level can shape how these nanostructures interact with living systems, which opens up interesting possibilities for how we think about designing future therapies.”
To evaluate whether αT modification altered the physicochemical properties of the DNA tetrahedrons, the researchers used dynamic light scattering (DLS), a technique in which a laser beam is passed through a liquid sample containing nanoparticles and fluctuations in the scattered light are analysed as the particles move randomly in solution. This enabled the researchers to measure the size and surface characteristics of nanoparticles in solution, providing insights into their stability, aggregation behavior, and potential interactions with biological systems.
Through cell culture experiments measuring cellular uptake and cytotoxicity, along with other mechanistic studies, the researchers found that attaching αT significantly enhanced the cellular uptake of DNA tetrahedrons, likely due to improved interactions with the fatty outer layer of the cell membrane. This was further supported by fluorescence imaging, which provided visual confirmation of greater accumulation of the modified nanostructures in cancer cells than in healthy cells, indicating preferential uptake by the former. Once inside, the αT-functionalised DNA tetrahedrons triggered the production of reactive oxygen species (ROS), causing oxidative stress and damage to DNA, proteins, and mitochondria. This ultimately led to programmed cell death, a controlled process in which damaged or unhealthy cells shut themselves down to prevent further harm to the body.
Lead author Ms P Chithra, an MTech student in the Department of Biological Sciences and Engineering, said, “What I found particularly encouraging was the consistency of the results across multiple experiments. Seeing a conceptual design translate into measurable biological outcomes is extremely rewarding and motivates us to continue developing more effective nanomedicine-based therapeutic strategies.” Reflecting on the broader significance of the study, Dr Raghu Solanki, Postdoctoral Fellow in the Department of Biological Sciences and Engineering and co-corresponding author of the work, commented, “One of the most exciting aspects of this research was observing how a simple design modification could significantly influence cellular behavior and therapeutic efficacy. Such studies highlight the immense potential of DNA nanotechnology and demonstrate how fundamental insights into cell–nanomaterial interactions can guide the development of safer and more effective targeted cancer therapies.”
While these findings demonstrate the potential of αT-functionalised DNA tetrahedrons as targeted anticancer nanocarriers, the research is currently limited to laboratory-based studies. Further investigations involving animal models, comprehensive safety evaluations, and clinical studies will be required to establish their therapeutic efficacy and translational potential. Nevertheless, by revealing how nanoscale surface modifications influence cellular uptake and biological responses, this work contributes valuable insights to the rational design of next-generation DNA nanomedicines and targeted cancer therapies.
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