Researchers have used a 3D model of a tumour and magnetically-driven nanomotor to probe the microenvironment of cancer cells. In the process, they said they have found a way to potentially target and kill tiny populations of cancer cells hidden within normal cells.
The researchers discovered that nanomotors would stick to the extracellular matrix near a cancer cell membrane more strongly than they would a normal cell. The extracellular matrix is a complex 3D network of proteins and carbohydrates secreted by living cells into their neighbourhood.
The discovery was made when scientists tried driving the nanomotors using an external magnetic field towards cancer cells in a tumour model and observed them getting stuck to a matrix near cancer cells. “But this was not observed near normal cells,” said Debayan Dasgupta, a co-first author and PhD student at the Centre for Nano Science and Engineering (CeNSE) at the Indian Institute of Science.
The original aim of the study was to sense, map and quantify changes in the cellular environment. The 3D model was made to comprise both healthy and cancer cells embedded within a reconstituted basement membrane matrix, and which mimics the breast cancer environment.
“This means that the cancer cells are doing something,” said Ambarish Ghosh, Associate Professor at CeNSE.
The reason why the nanomotors appear to stick to the cancer cells better is due to their negatively charged extracellular matrix. This may be due to the presence of 2,3-linked sialic acid, a sugar-conjugated molecule which confers a negative charge on the cancer cell environment, researchers found.
“In the end, we really ended up discovering a physical property of an important biological environment,” Dr Ghosh said.
Using fluorescent markers, the scientists found that sialic acids were distributed up to 40 micrometres from the cancer cell surface ‒ the same distance until which the nanomotors experienced strong adhesion.
“What came as a beautiful surprise was that within such a milieu, we found that aggressive cancer cells ended up remodelling their surroundings by making them stickier, and richer in specific charged sugars,” says Ramray Bhat, Assistant Professor at the Department of Molecular Reproduction, Development and Genetics (MRDG), and one of the senior authors.
“This charging can potentially be used to target and kill tiny populations of cancer cells hidden among their normal counterparts, for which we are extending these studies to living animals,” he added.