Cell and organelle mimics typically perform one simple function. Frank Caruso and team at the University of Melbourne, Australia, contemplate more complicated systems

Artificial cells and organelles are expected to become powerful therapeutic tools to perform missing or lost cell functions - essentially to make, convert or degrade biomolecules. Amongst their potential applications, replenishing absent or malfunctioning enzymes is a valuable goal as this might provide a long-term solution for chronic diseases. But the field is still in its infancy, with the most successful examples of synthetic cells and organelles typically performing only a single, simple function. 

Nevertheless, recent efforts have led to substantial improvements in the design of these synthetic microreactors. In particular, advances have been seen in more structurally stable scaffolds to house the synthetic machinery, enhance reagent and nutrient exchange between the vessels and their surrounding environment, and in introducing subcompartments within the vessels, allowing researchers to conduct multiple, spatially separated and/or continuous reactions.

Synthetic mimics (left) can share many similarities with biological cells (right)

The field has also been boosted significantly by the advent of polymer capsules assembled by layer-by-layer techniques. In this procedure interacting polymers are deposited sequentially onto a sacrificial colloidal template which is eventually removed. Two prominent polymer pairs that form stable, micrometre- or smaller-sized capsules are based on poly(allylamine hydrochloride)/polystyrene sulfonate and poly(N-vinyl pyrrolidone)/poly(methacrylic acid). While the former capsules are not biodegradable and have potential use in creating organelles with extended lifetimes, the latter polymer pair is used to obtain biodegradable capsules stabilised by deconstructible disulfide linkages. 

Progress in cargo loading has meant that peptides, nucleic acids and intact proteins can be trapped inside such polymer capsules, making them particularly promising candidates in the design of therapeutic artificial cells and organelles. The first examples of enzymatic reactions within the capsules have brought these vehicles one step closer towards this. The most well studied class of these reactions involves the enzyme-catalysed conversion of small molecules, as the capsules' semipermeable nature allows small substrates and products (for example ions) to diffuse in and out while the larger macromolecules are blocked. 

A number of enzymes have now been successfully encapsulated, retained their activity and performed their function within capsules. We recently reported DNA degradation triggered by a nuclease within a polymer capsule, a function reminiscent of that of the cellular lysosome, an organelle containing several digestive enzymes. This was one of the first examples of a layer-by-layer assembled capsule mimicking an organelle.

A nature-inspired approach towards synthetic reactors that allow multiple, spatially separated and parallel reactions, requires that the vessels be subdivided. Specific examples include two-compartment polymer capsules, smaller lipid or polymeric vesicles embedded in larger vesicles, and smaller capsules embedded in cross-linked gel beads. 

We have developed an approach to obtain polymer carrier capsules with thousands of liposomal subcompartments (see green spherical structures in figure). Termed capsosomes, these vehicles preserve the positive features from both systems - the polymer hydrogel carrier capsule provides a structurally stable scaffold, while the liposomal subcompartments trap and protect small and/or fragile biomolecules. Capsosomes can retain a model enzyme and preserve its activity for at least two weeks. 

The progress in the design of layer-by-layer-derived polymer capsules, including the choice of building blocks to obtain stable capsules, the creation of subdivided systems, and the successful encapsulation of enzyme-catalysed reactions, illustrate the potential of these vehicles as synthetic cell and organelle mimics. While many challenges still need to be addressed, including creating systems that can self-replicate, self-repair, and recognise a target, the field is undoubtably on the verge of creating medically relevant examples. 

Read more in the Minireview 'Polymer hydrogel capsules: en route toward synthetic cellular systems' in Nanoscale.

Enjoy this Instant insight? Spread the word using the 'tools' menu on the left or add a comment to the Chemistry World blog.