| Sunitha Nagrath
Pic: Joseph Xu
For several years now, Sunitha Nagrath, India-born chemical engineer in the US, has been honing her skills to develop devices that could detect trafficking — trafficking of a different kind, though. She wants to hunt down the first set of cancer cells that dislodge themselves from a tumour and migrate to a distant part of the body to initiate metastasis, a complex process of spreading cancer to a secondary site.
Spotting these circulating tumour cells (CTCs) can help identify patients at risk for metastasis early on, but, unfortunately these wandering cells are extremely rare, making their identification a daunting task.
Currently there is no cure for most types of metastatic cancer but they can be managed by limiting the growth of the tumour. This is why early detection of CTCs is vitally important.
In a paper published online in the journal Nature Nanotechnology yesterday, Nagrath and her colleagues at the University of Michigan at Ann Arbor in the US announced the development of a novel nanomaterial-based chip that can identify CTCs that get detached from the existing tumour and are carried through the bloodstream to other organs. Despite their numbers being few, these cancerous cells are distinguished from healthy blood cells by the graphene-oxide-based device and analysed for cancer-related biomarkers.
If they are successful in repeating in humans what they have achieved in the lab, cancer hospitals around the world will be able to establish a person’s chances of developing metastatic cancer by just doing a blood test. Limited trials that have been conducted with blood drawn from early-stage lung cancer patients as well as advanced metastatic cancer patients have already demonstrated the potential of the device.
Such devices can also be useful in checking whether a patient is responding to treatment well, says Vinod Raina, head of medical oncology at the Fortis Memorial Research Institute in Gurgaon. “During active disease, these tumour cells will be in circulation in many cancers. During the treatment, their numbers are expected to go down or disappear completely. Once available for clinical use, this can be helpful in recording the progress that the patient is making,” he says. Similarly, it can also be used to detect early recurrence, explains Raina, who was former head of medical oncology at the All India Institute of Medical Sciences, New Delhi.
The scientists led by Nagrath, who was born and brought up in Nellore in Andhra Pradesh before moving to the US, chemically prepared the graphene oxide nanomaterial — tiny two-dimensional sheets — to capture the CTCs by binding to them certain molecules (antibodies) that can attract these malignant cells.
“These antibodies are highly specific and they can bind to molecules found outside the cells. CTCs are known to express certain molecules, so we selected the antibodies accordingly,” Nagrath told KnowHow.
“The surface patterning of the nano-chip is very cleverly done to ensure that almost all the cells in the blood samples come into contact with antibody molecules bound to the surface,” says Manzoor Koyakutty, senior researcher at the Amrita Centre for Nanosciences in Kochi who is not connected to the study.
|An illustration showing how CTCs are formed
Metastatic cancer has the same name and the same type of cancer cells as the primary cancer. For instance, breast cancer that spreads to the lung is metastatic breast cancer in the lung, not lung cancer.
To conduct the experiment, the scientists used breast, lung and pancreatic cancer cells cultured in the lab. Known quantities of these cancer cells were subsequently mixed in blood for testing the sensitivity of the device.
Nagrath says establishing sensitivity (that is, the ability to spot CTCs) with a low number of targeted cells is a huge challenge. “In our study, we have been able to recover 94 per cent of the 100 cells that were spiked into blood, whereas recoveries were 87 per cent and 73 per cent, respectively, for 10-20 cells and 3-5 cells (spiked into blood) respectively,” says Nagrath, who did her BTech from Sri Venkateswara University, Tirupati, 16 years ago. She has been working to develop smart chips that can detect cancer for a while and won a grant from the US National Institutes of Health in 2009.
Nagrath, however, feels more work is needed to establish the potential of this specific device. “It is too early to rank this device relative to other detection technologies in terms of sensitivity. However, we are very optimistic about the potential of nanomaterials (in early cancer detection),” she says.
Indian scientists working in the field of nanomedicine think the work may open a new avenue for early detection of metastatic cancer. “It is still in a very early stage but the results they achieved are quite comparable to those produced by the methods currently employed,” says Gopinath Packirisamy, assistant professor at the Indian Institute of Technology, Roorkee, whose studies have shown that nanoparticles can be used to diagnose and treat lung cancer.