Snailing colorectal cancer drug delivery, once and for all
Inspired by snails, a new drug delivery project has received a considerable funding boost.
As any gardener can tell you, nothing possesses the ability to strike fear into your heart like the slow, remorseless march of a leaf-seeking snail, precision-targeted to the most vulnerable and delicious plants, as my dear lupins can attest. Scatter as many eggshells as you like; they shall not relent. Now, thanks to a research grant awarded to a multidisciplinary team of University of Manchester (UK) researchers, led by aerospace engineer Mostafa Nabawy, cancer cells may soon know this fear.
Cancer therapies are becoming increasingly advanced, but off-target, systemic effects still pose serious complications for doctors and patients alike, making the delivery of a critical dose to the site of a tumor challenging to achieve without inducing adverse effects in the patient.
In order to address this issue, the UK Research Institute’s (UKRI; Swindon, UK) Cross Research Council Responsive Mode scheme, which supports interdisciplinary projects, has awarded a University of Manchester research project with almost £1 million in funding to produce a delivery method that enables highly targeted drug release directly at tumor sites. The pitch is co-led by Mostafa Nabawy (owning robotics), Mohamed Elsawy (owning bionanomaterials), William Sellers (owning biomechanics), Katie Finegan (owning cancer biology) and Lee Margetts (owning digital twins).
The pitch that caught the UKRI’s eye was inspired by snails, specifically their movement. When asked the obvious question by BioTechniques: “why snails?” Mostafa explained that “gastropod molluscs such as snails use slime-based locomotion and can survive in extreme environments, including as intestinal parasites, and we believe this body plan is ideal for our application. Their locomotor mechanism provides high precision, low speed, and substrate-independent body movement, which will enable regiospecific localised drug release, for enhanced bioavailability in malignant tumours.” Essentially, the team want to create mini robots, starting at the centimeter scale, that they can direct through the gastrointestinal tract to the site of colorectal cancer tumors, before triggering a release of the therapeutic payload, increasing bioavailability and reducing off-target effects.
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Speaking to BioTechniques about their selection of payload, Mostafa revealed that they intend to focus on “targeted small molecule drugs, such as protein kinase inhibitors (PKIs), which have shown great potential as they selectively target the aberrant PK activation associated with tumour growth and progression in different cancer types, including colorectal cancer (CRC). However, most developed PKIs have poor tumour bioavailability, requiring high doses for efficacy, and often cause severe off-target effects, necessitating dose reduction or treatment cessation. Despite recent endeavours with PKI-targeted drug delivery, innovative approaches are still needed to allow localised dosing, minimise side effects, and enable a drastic change in how we use PKIs to help cancer patients.”
First, the team will need to find out more about how snails move, as the biomechanics of snail locomotion remain fairly loosely understood. To do this, they will produce the first high-resolution data set on snail movement, food actuation and mucus interactions with which they can train digital simulations and machine-learning-based control systems.
These simulations can then inform the design of biocompatible, peptide-based soft robots, engineered to respond to bioinert external signals, such as magnetic fields, to enable their remote control. This will be coupled with the design of a digital twin simulation framework to enable the rapid testing of designs in silico, reducing costs and accelerating the pace of development.
Commenting on the team’s aspirations for the project, Mostafa stated that their research “…brings together biology, materials science and robotics in a way that could genuinely transform future cancer therapies. By studying these remarkable organisms and translating their movement strategies into soft robotic systems, we hope to deliver a step change in how medicine is administered deep inside the body.”
There is no reason, if this project proves successful, that these findings will only apply to colorectal cancer, or even cancer more broadly, and the team are already considering the potential application of these robots in clinical endoscopy, environmental, agricultural and industrial processes.