In the field of identifying cancer cells, an interdisciplinary team of researchers from the Indian Institute of Science (IISc) has made a breakthrough. They developed a technique using a 3D tumor model and magnetically driven nanomotors to examine the microenvironment of cancer cells.
The team has researchers from the Centre for Nano Science and Engineering (CeNSE) and Department of Molecular Reproduction, Development and Genetics (MRDG).
A beautiful surprise
Ramray Bhat, Assistant Professor at MRDG, and one of the senior authors observed, “What came as a beautiful surprise was within such a milieu the team found that aggressive cancer cells ended up remodelling their surroundings. They have made them stickier and richer in specifically charged sugars”.
He said, “Using the charging to target, we can kill the tiny populations of cancer cells hidden among their normal counterparts. For this we are extending our examination to living animals.
In their work published in Angewandte Chemie, the team has guided helical nanomotors remotely. They steered this via an external magnetic field through the tumour model. Using that they can sense, map and qualify changes in the cellular environment.
To study the extracellular environment of cancer
The team said in the journal, “We believe identifying cancer cells will find use as targeting strategies in future in vivo applications. Also, we believe in qualifications of cancer aggressions and as biophysical probes to study the extracellular environment of cancer”.
The paper published by Angewandte Chemie said, “The model includes both healthy and cancer cells embedded within a reconstituted basement membrane matrix. And mimics the breast cancer surrounding.
Debayan Dasgupta, the co-author and PhD student at CeNSE said,” We tried driving the nanomotors towards these cells in a tumour model. We have observed that these cells get stuck to the matrix near cancer cells. But near-normal cells exhibited this.”
A complex 3D network
“The extracellular matrix (ECM) is a complex 3D network of proteins and carbohydrates. They are secreted by living cells into their neighbourhood surrounding”, the IISc note further claimed. However, when these cells secrete fresh material into the ECM, it disrupts the chemical and physical composition of the native ECM environment healthy cells. Moreover, It degrades the local surrounding. As a result of this, understanding how the cancer cells do alteration to the cellular microenvironment. However, for the understanding of the progression of cancer, measuring these changes is vital, Dasgupta added.
Calculation by the team
Recent studies have shown that the nanomotors approached the cancer cell membrane and stuck to the matrix more strongly than they would to normal cells. The team calculated the magnetic field strength required to overcome the adhesive force to measure how strongly the nanomotors bind to the matrix and move forward.
Ambarish Ghosh, Associate Professor at CeNSE and one of the senior authors explained, “This means that the cancer is doing something. As a result of this, we carried out some research. But, only to find out that the adhesive force depended on the type of cells. Accordingly, We have discovered the strength of interaction and also which side of the cell the nanomotor approached”. In the end, we really ended up finding the physical property of an important biological environment.
Reason of nanomotors sticking to cancer cells
The researchers discovered the reason for the nanomotors sticking to the cancer cells better is a result of changed ECM. However, this may be because of the presence of 2-3 linked sialic axis, a sugar conjugated molecule. Which confers a negative charge on the cancer cell surroundings. Also, The team visualized the distribution of sugar molecule using fluorescent markers. They found that sialic acids spread up to 40 micrometers from the cancer cell surface.
The team coated the nanomotors with Perfluorooctyltriethoxysilane (PFO) which shielded them from charged surrounding to counter adhesive effect.
“We have shown how we can use the investigation of manoeuvrability of the nanomotors. Spatially to differentiate between cancerous cells and non-cancerous cells niches. Moreover, It can coexist within tissue-like surroundings” Prof Ghosh added.