Engineering the future of cancer treatment
17 October 2016
Of the many new developments in cancer research, one of the most promising comes from nanoscience. Bioengineers are designing nanoparticles that can deliver treatments and diagnostics directly to tumours, raising the prospect of much more precise and effective interventions.
However, the behaviour of each nanoparticle varies depending on several factors, including its size, shape, coating and cargo, and on the interactions in the body that result. And when trillions of such nanoparticles are involved in each case, their collective behaviour in the complex environment of a tumour is crucial to the success of the treatment. But that behaviour can be difficult to predict.
For example, nanoparticles can be engineered to accumulate specifically in cancer cells, but may only accumulate in the first cells they encounter rather than penetrating further into the tumour. Similarly, particles delivered via a technique known as convection-enhanced delivery (CED) may not accumulate in the right concentrations throughout the tumour to be effective.
‘Estimating which designs will lead to the desired outcomes in specific cases has proved far from straightforward,’ says Dr Sabine Hauert in the Department of Engineering Mathematics. ‘One of the biggest challenges is to find an accurate way to visualise the behaviour of nanoparticles, since neither in vitro nor in vivo experiments provide enough detail.’
One possible solution emerged at a workshop organised by Dr Hauert and hosted by the Elizabeth Blackwell Institute. Its purpose was to consider clinical applications for nanomedicine, explore the design and testing of micro-nano systems, and discuss future opportunities in swarm engineering.
As a direct result of the discussions with other colleagues at the event, Dr Hauert drew up a proposal for a cross-disciplinary project, bringing her together with other speakers from the day (Dr Andy Collins, School of Physics, Dr Adam Perriman, School of Cellular and Molecular Medicine, and Mr Barua and Dr Bienemann, Southmead Hospital, Bristol). With a grant from the Elizabeth Blackwell Catalyst Fund, they began their work, the centrepiece of which was a microfluidic testbed for studying the dynamics of nanoparticles in tumour-like environments.
First, Dr Hauert and her colleagues developed a preliminary computational model that would predict tissue penetration in brain tumours depending on variables such as nanoparticle injection speed, drainage, and binding properties. The team also built up a small library of fluorescent nanoparticles (fluospheres), each with well-defined properties and designs, for use on their newly designed microfluidic testbed.
Using gelatin to simulate the tissue-like environment, they were able to monitor the distribution of nanoparticles under a microscope, and to capture it on high-definition video. Preliminary experiments were also performed in in vivo (rat brain) using quantum dots and pluronic micelle nanocarriers. Results showed the clear impact of nanoparticle charge on their anchoring in the brain tissue. This provides a promising indication of the best designs for treatment.
The project’s success is due in no small part to the strong connections made possible by the Elizabeth Blackwell Institute’s cross-disciplinary network of researchers. The core team combined Bristol expertise in computer modelling (Sabine Hauert), nanoparticle design (Andy Collins, Adam Perriman), and microfluidics (Sabine Hauert, Andy Collins, Adam Perriman); when the guidelines they had developed were ready for testing in vivo, they worked with Professor Steven Gill, Consultant Neurosurgeon, Southmead Hospital, and his team in the School of Clinical Sciences – the most experienced team in the world when it comes to the clinical use of direct drug delivery to the brain using CED.
The work of Dr Hauert and her team has also, in its turn, consolidated and developed collaborative ties with researchers and clinicians, both at Bristol and beyond. Partnerships are planned with colleagues in the School of Cellular and Molecular Medicine and the School Veterinary Sciences; and the EBI-funded project formed the basis for a recent Horizon 2020 FET-Open bid on the use of nanoparticles to target cancer stem cells – work that would involve partners from the UK, Spain, Portugal, Serbia and Finland. Further collaborations are also planned with researchers at MIT and Harvard University. The team have also been invited to submit a full proposal for the Cancer Research UK Multidisciplinary Project Award.