Using phosphatases to generate self-assembled nanostructures and their applications

Self-assembled nanostructures have received significant research interest in the last decade, because they show great promise for drug delivery, diagnostics, tissue engineering, and regenerative medicine. Recently, the development of enzyme-assisted self-assembled nanostructures has become an active area of research because of the attractive characteristics of enzymes, such as ready availability, good biocompatibility, and high selectivity and specificity. Phosphatases, taking part in approximately 30% of intra- and extracellular activities, have been widely employed as triggers for the generation of self-assembled biomaterials, including static, reversible, and dynamic systems.

In this review, we highlight the generation of self-assembled systems of synthetic molecules using phosphatases and their potential applications. We first summarize the generation of different kinds of static and dynamic self-assembled structures, including nanofibers and nanoparticles, by the dephosphorylation reaction catalyzed by phosphatases. The antagonistic interactions of phosphatases and kinases make this system one of the most attractive candidates for biotransformation. Diverse biomedical applications of phosphatases/kinases-involved self-assembled systems have been extensively explored in fields such as bacterial growth inhibition, drug delivery, imaging of self-assembly inside live cells, and biomineralization. We then summarize the reversible self-assembled systems controlled by the pair enzymes of phosphatases/kinases, in which different morphologies of self-assembled nanostructures can be achieved and switched by the pair enzymes. These phosphatase-involved self-assembled systems can be used for many applications such as controlled drug delivery, enzyme activity imaging, and cancer cell inhibition.

Phosphatases are over-expressed in several cancer cell lines. Their detection is, therefore, important for cancer diagnostics. Nanomaterials that can respond to abnormal phosphatase activities also have big potential for the delivery of therapeutic agents on demand. The study of reversible self-assembling systems control by the phosphatase/kinase switch may provide useful insights to understand the working principle of this important biological switch.

The design principle mentioned in this review may stimulate the generation of smart self-assembled systems by other enzymes or other pairs of enzymes. The combination of environment-sensitive fluorescence property of fluorescent dyes and self-assembling molecules that can respond to enzymes may lead to the development of smart probes to monitor important biological processes.