Peptide-triggered particles that release cargos when they meet an enzyme could find use delivering drugs in the body. 

The system, developed by Rein Ulijn from the University of Strathclyde, UK, and colleagues, consists of hydrogel particles with branched peptide structures called actuators embedded throughout. The particles can be loaded with a payload such as a drug molecule. 

Hydrogel microparticles swell when an enzyme cleaves attached peptide actuators

When Ulijn's hydrogel particles encounter a protease - an enzyme that hydrolyses peptide bonds - the attached peptide actuators are cleaved. The result is a switch in the actuators' charge balance, from neutral to positive, causing the particles to swell to reduce repulsion between the positive charges. The payload can then diffuse out of the particles through the polymer mesh. 

Many existing enzyme responsive systems work by hydrolysing covalent linkers between a polymer carrier and its payload. Ulijn says that the advantage of trapping the payload physically, as in his method, is twofold. It avoids chemically coupling the payload and polymer, which may require conditions incompatible with protein payloads. Also, existing systems allow only one payload per linker. 'In our system the number of payload molecules is variable relative to the number of peptide actuators,' Ulijn says.

Whilst Ulijn has used actuators to control hydrogel particles before, the linear actuators he used did not cause the particles to swell at physiological ionic strength, crucial if the system is to be ever to be used to deliver drugs in vivo. 'We had to think of a way to overcome this,' Ulijn says, 'which we did by enhancing the charge density using branched actuators.' These actuators are converted into four cationic groups instead of the two produced by the linear versions. This causes the particles to swell more, allowing triggered payload release at physiological ionic strength. 

Jiandong Ding, an expert in biomedical polymeric materials, from Fudan University, Shanghai, China, says 'the success under physiological conditions is encouraging. It shows the potential of this intelligent platform in pharmaceutical applications,' he adds.

The team's future efforts will be focused on developing a reversible system using a combination of complementary enzymes. 'This could be potentially used as a biomimetic motor,' says Ulijn, 'as it would be able to swell and collapse in response to a molecular fuel such as ATP.'

Alexandra Haywood

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