Researchers from the Biodesign Institute at Arizona State University (ASU) in the USA and from the National Centre for Nanoscience and Technology (NCNST) in China, collaborated to develop DNA nanorobots which travel the bloodstream and find tumours. Once tumours are located, the nanorobots are programmed to deliver a protein which causes the blood supply of the tumours to be blocked, thus leading to their 'starvation' and shrinkage.
'These nanorobots can be programmed to transport molecular payloads and cause on-site tumour blood supply blockages, which can lead to tissue death and shrink the tumour,' said Professor Baoquan Ding from the NCNST, one of four lead authors of the study.
The research, published in Nature Biotechnology, found that DNA nanorobot treatment successfully led to shrinkage of a variety of different tumour types in mouse cancer models, as well as preventing cancers from spreading. Treated mice were also found to survive 1.5-2 times longer than untreated ones.
The nanorobots are designed as flat sheets of DNA, which can be loaded with a blood-clotting enzyme known as thrombin. The DNA sheets are folded into tubes, hiding thrombin in the centre. On the outside of the tubes are 'DNA aptamers' - structures which recognise and bind to specific tumour proteins (not found of the surface of healthy cells). Once tumours are located by the DNA aptamer binding, the tube unfolds, leading to the release of thrombin, triggering blood clotting and tissue death.
This strategy could have advantages over traditional treatments such as chemotherapy or radiotherapy, as the killing activity is very specifically restricted to tumours – no other cell types or tissues were affected in the mouse models. This could lead to a reduction in side effects.
The authors tested their DNA nanorobots for safety in Bama miniature pigs, closer to humans in physiology than mice, checking that they did not induce an immune response or cause random blood clotting events. 'The nanorobot proved to be safe and immunologically inert for use in normal mice and, also in Bama miniature pigs,' said Professor Yuliang Zhao from the NCNST.
Although the research is still far from clinically relevant, it represents a significant advance in the field of nanomedicine. 'I think we are much closer to real, practical medical applications of the technology,' said Professor Hao Yan from ASU, a lead author on the study. 'Combinations of different rationally designed nanorobots carrying various agents may help to accomplish the ultimate goal of cancer research: the eradication of solid tumours and vascularised metastases.'