6 Jan 2018
A new hydrogel programmed to release therapeutics in response to environmental cues has been developed by researchers at the University of Washington, US.
The biomaterial-based delivery system is made by introducing ‘cross-link’ gates into a polymer network that, once triggered by certain physiological conditions, releases its cargo.
‘Our “gates” consist of chemical chains that could – for example – be cleaved only by an enzyme that is uniquely produced in certain tissues of the body; or be opened only in response to a particular temperature or specific acidic conditions,’ said Cole DeForest, team leader and Assistant Professor of Chemical Engineering at the university.
‘With this specificity, we realised we could more generally design hydrogels with gates that would open if only certain chemical conditions – or logic statements – were met.’
Improved specificity in drug delivery systems are increasingly sought after in the pharmaceutical industry to help reduce off-target effects.
The hydrogel’s gates are programmed on the principles of Boolean logic, for which all values are either true or false, allowing for increased specificity. For example, a gate developed by the team was designed as a short peptide, which can be cleaved by the enzyme matrix protease (MMP). If MMP was absent, the gate would remain intact and the cargo would not be released.
‘The modular strategy that we have developed permits biomaterials to act like autonomous computers,’ said DeForest. ‘These hydrogels can be programmed to perform complex computations based on inputs provided exclusively by their local environment. Such advanced logic-based operations are unprecedented, and should yield exciting new directions in precision medicine.’
Researchers built hydrogels based on three simple principles: ‘YES’, ‘AND’ and ‘OR’. Those programmed with ‘YES’ cross-link gates only opened when a specific environmental condition was met – for example, the presence of a certain enzyme or acidic state.
Gates programmed with the ‘AND’ function add a higher level of specificity still, where multiple conditions must be met for the gate to open. The team tested this function with a hydrogel carrying the chemotherapy drug doxorubicin, only released in the presence of a reductant (an element or compound that donates an electron to another chemical species) and MMP.
The hydrogel was placed in a culture of HeLa cells, which are found in cancerous tumours and commonly used in scientific research.
The team found that the HeLa cells survived and the doxorubicin remained in the hydrogel unless both conditions were met. Each of the cues alone also could not open the gate.
‘Our hope is that, by applying Boolean principles to hydrogel design, we can create a class of truly smart therapeutic delivery systems and tissue engineering tools with ever-greater specificity for organs, tissues or even disease states such as tumour environments,’ said DeForest.
‘Using these design principles, the only limits could be our imagination.’
Nature Chemistry, DOI:10.1038/nchem.2917
By Georgina Hines