Synthetic enzymes for controlled drug delivery in cells

The Nanoscopy for Nanomedicine group has studied Single-Chain Polymeric Nanoparticles (SCPNs) mimicking enzymes as possible drug activators in biological environments, like the living cell.

The bio-inspired nanoparticles could be used to spatially control drug delivery in the treatment of diseases such as cancer.

Through their study, published in JACS, the researchers have optimized the delivery strategies of dynamic SCPNs so that they retain their catalytic activity at the cellular environment. This paves the way towards the rational design of nanosystems that can perform effective catalysis in vivo.

Read more…

Image: SCPNs triggering fluorescence locally (in green) by activating a pro-fluorophore molecule.

SCPNs are nanometer-sized objects inspired in the way enzymes work; they carry a catalyst which is activated when the structure is folded. Although artificial enzymes had been reported before, this study is the first to demonstrate their viability in complex environments such as the cell. “Shielding in SCPNs is a non-toxic, biocompatible way of containing a synthetic catalyser working in harmony with what’s already going on in the cell,” says Silvia Pujals, a postdoc in Lorenzo Albertazzi’s group at IBEC. “In other words, it doesn’t interfere with the normal behaviour of cells.”

The SCPNs under study can be delivered intracellularly or extracellularly depending on the envisioned application. For photodynamic therapy (PDT) applications an intracellular delivery is needed while organometallic catalysts work well extracellularly. This last application of SCPNs is for controlled drug delivery. For example, the synthetic enzymes could activate anti-tumour drugs delivered through the blood stream just at the tumour area. “So far, we have obtained promising results by locally activating a fluorophore with the SCPNs as catalysts just at the SCPN exposed areas,” says Lorenzo. “We believe that these enzyme-like nanoparticles could be used for their pro-drug activity in different biomedical applications.”

Source article: Yiliu Liu, Silvia Pujals, Patrick J.M. Stals, Thomas Pauloehrl, Stanislav I. Presolski, E. W. Meijer, Lorenzo Albertazzi, and Anja R.A. Palmans (2018). Catalytically Active Single-Chain Polymeric Nanoparticles: Exploring Their Functions in Complex Biological Media. J. Am. Chem. Soc., 140(9):3423-3433