Conventional cancer treatments, such as chemotherapy, often damage both cancerous and healthy cells, leading to severe side effects. As an alternative, scientists have explored DNA nanotechnology, which involves engineering DNA into nanoscale structures capable of carrying drugs, imaging agents and therapeutic molecules. Among these, DNA tetrahedrons have attracted attention due to their biocompatibility, low tendency to provoke immune responses, and the ability to be easily customised for different therapeutic purposes. However, their therapeutic potential is often limited by inefficient cellular uptake and restricted intracellular delivery.
To overcome these challenges, researchers at IITGN modified DNA tetrahedrons by attaching alpha-tocopherol succinate (ฮฑT), a Vitamin E-derived molecule that can disrupt vital functions inside cancer cells while acting protectively in healthy cells, ensuring specificity and improved anticancer efficacy. Analysis of the size and surface characteristics of these modified nanostructures further showed that ฮฑT altered these properties while preserving structural integrity, suggesting improved interactions with cell membranes. Supporting this observation, cell culture experiments, cytotoxicity studies and fluorescence imaging revealed enhanced uptake of the modified nanostructures by cancer cells. Once taken up by the cells, they triggered the production of reactive oxygen species (ROS), leading to oxidative stress and damage to cellular DNA, proteins and mitochondria, ultimately causing the cancer cells to self-destruct, a process called programmed cell death.
By uncovering how subtle nanoscale modifications can shape cellular behaviour, this work offers valuable guidance for the development of next-generation DNA nanomedicines and targeted cancer therapies.
The team includes P Chithra, Ankesh Kumar, Dr Payal Vaswani, Dr Raghu Solanki, and Prof Dhiraj Bhatia.
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