February 12, 2018

expert reaction to study looking at DNA nanorobots to target cancer in mice and pigs

A new study, in Nature Biotechnology, investigates the use of nanorobots to shrink tumours by cutting off their blood supply.

Prof. Terry Wilkins FREng, Emeritus Professor of Nanomanufacturing Innovation, University of Leeds, said:

“It is lovely new science and stands on its merit.  It seems to be a welcome addition to what those of us involved in targeted drug delivery research for the last 10 years would recognise as part of this field.

“The use of the terms ‘nanobots’ and ‘nanorobots’ is unfortunate.  The term ‘robot’ tends to be applied to mechanical devices with or without autonomous intelligence.  I recall the great Isaac Asimov’s views on robots and how to make them safe and ethical.  We are far from his definition with respect to this valuable research.

“Notwithstanding, my best wishes go out the researchers.”

Prof. Andrew Sharrocks, Professor of Molecular Biology, University of Manchester, said:

“This looks like very clever technology which can specifically target and destroy tumour cells in this animal work.  As tumour-specific targeting of ‘payloads’ is one of the more difficult things to achieve, this looks to be a very interesting advance in this area in the fight against cancer.  However, I think that calling these delivery particles ‘nanorobots’ is over-hyping and is not accurate, and could actually cause more alarm than excitement.”

Prof. Khuloud Al-Jamal, Professor in Nanomedicine, King’s College London, said:

“This is an interesting piece of work by the Zhao group of the National Center for Nanoscience and Technology, China.  The clever part of this DNA-based nanorobot design is the fact that binding the targeting DNA to a receptor (nucleolin), which is more abundant in the vasculature of the tumour, causes the collapse of the nanorobot.  Subsequently the release of the drug, which in this case is a clotting protein called thrombin, causes formation of blood clot in the tumour followed by shut down of the blood supply and tumour death.  The system clearly works, as shown by reduced tumour volumes.  The main concern however is how to rescue healthy tissues that may still have this receptor expressed as part of its healthy function.”

Dr Peter Bannister, Chief Technology Officer of Median Technologies and Chair of the Institution of Engineering and Technology’s Healthcare Sector, said:

“Despite advances during the past years in robotic surgery and precise tissue characterisation, there remains significant challenges in accurately and routinely defining surgical margins and delivering therapies in a predominantly non-invasive manner, which would reduce patient risk and overall costs.  These pre-clinical results are encouraging and demonstrate a fascinating approach to bringing improved patient outcomes that would enable rapid advances in precision medicine and therapeutic stratification in the future.”

Prof. Dorothy Bennett, Director of the Molecular and Clinical Sciences Research Institute, St George’s, University of London, said:

“This report combines several clever molecular design aspects to impair cancer growth in animal models.

“There have been several experimental approaches to cancer treatment that have been called nanorobots or nanobots, from various groups around the world.  These have little resemblance to robots but are synthetic molecules designed to recognize a molecule and then do something.  (In this sense, most enzymes could rate as nanorobots).

“The press release seems to describe the report with reasonable accuracy, and the work seems solid, though one might view some of the language as overblown.  These particular ‘robots’ are rolled sheets made of DNA and they are ‘programmed’ by attaching another molecule to them that will recognize the inside of growing blood vessels.  When they recognize their target, the sheet unrolls to release molecules of thrombin the natural trigger for blood clotting.

“The clever ideas include (1) recognising the cancer blood vessels rather than actual cancer cells, since the vessels are what a circulating molecule would meet first, rather than having to get outside the bloodstream and find the cancer cells there; and also this is not limited to a single cancer type; and (2) triggering blood clotting to cut off the cancer’s blood supply.  (Note: previous work from Durham involved ‘nanorobots’ that recognised actual cancer cells and drilled a hole in the cell to kill it, so this approach is different.)

“This could potentially have a therapeutic effect in adults with cancer, where generally there will not be any newly forming blood vessels except within the growing cancer.  It would not presumably be specific enough if there were any other growing blood vessels present, for example in growing infants or in people with healing wounds.

“It should be noted that the report involves only cells and mouse models, and only in one kind of cancer out of four were some animals apparently completely cured.  In the others the cancer growth was only delayed.  It is hard to predict what might happen in human cancers.”

Prof. Peter Dobson, The Queen’s College, University of Oxford, said:

“This paper has some very clever and elegant ideas.  It is written in a style that most outside of the field will struggle to understand and it is unfortunately using terms such as ‘DNA nanorobot’.

“They have used an idea of making a carrier from DNA, like a little parcel, to carry thrombin to a tumour and this little ‘parcel’ unfolds when it encounters the tumour site and releases the thrombin which will coagulate the local blood supply to the tumour causing it to die.  It is a neat idea and there is a lot of evidence in the paper to show that this is a promising approach.  It should be said that it has only been done so far in animals.  The authors state in the paper that they have done experiments in Bama miniature pigs that have similarity to humans in terms of anatomy and physiology.”

* ‘A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo’ by Suping Li et al. published in Nature Biotechnology on Monday 12 February 2018.

Declared interests

Prof. Terry Wilkins: “I have no interests to declare here.”

Dr Peter Bannister: “Peter is Chief Technology Officer of Median Technologies (full-time employee) and holds a volunteer position as Executive Chair of the IET’s Healthcare Sector.”

Prof. Dorothy Bennett: “No conflict of interest.”

Prof. Peter Dobson: “I have no declaration of interests to make.”

None others received.