Supramolecular catalysis and dynamic assemblies for medicine

Abstract

In this review, supramolecular catalysis refers to the integration of catalytic process with molecular self-assembly driven by noncovalent interactions, and dynamic assemblies are the assemblies that form and dissipate reversibly. Cells extensively employ supramolecular catalysis and dynamic assemblies for controlling their complex functions. The dynamic generation of supramolecular assemblies of small molecules has made a considerable progress in the last decade, though the disassembly processes remain underexplored. Here, we discuss the regulation of dynamic assemblies via self-assembly and disassembly processes for therapeutics and diagnostics. We first briefly introduce the self-assembly and disassembly processes in the context of cells, which provide the rationale for designing approaches to control the assemblies. Then, we describe recent advances in designing and regulating the self-assembly and disassembly of small molecules, especially for molecular imaging and anticancer therapeutics. Finally, we provide a perspective on future directions of the research on supramolecular catalysis and dynamic assemblies for medicine.

Assemblies of Peptides in a Complex Environment and their Applications

“…While the assemblies of peptides, forming by instructed assembly in situ, in a complex environment, and their applications are emerging as a promising frontier of peptide research, several challenges remain: i) The lack of high‐resolution tools for monitoring the dynamics of the peptide assemblies in live cells over a large area and extended time; ii) The lack of comprehensive quantitative analysis for correlating the functions and kinetics of peptide assemblies, though a recent quantitative analysis of the instructed assembly of peptides in cells started to elucidate the relationship between instructed assembly and cancer‐cell death; iii) The lack of guiding principles to combine different triggers to provide more sophisticated applications; iv) The lack of understanding of the large‐scale behavior that emerges from peptide assemblies, although both nanoscale processes and microscale phenomena now are observable. Despite these challenges, we expect the advances of knowledge from different disciplines and the development of tools will gradually address these issues since they are rather generic and similar to the challenges in understanding the functions of biomacromolecular assemblies in living organisms.…”

Enzyme‐Instructed Supramolecular Self‐Assembly with Anticancer Activity

“…To date, a significant number of enzyme responsive assembling precursors have been prepared . Subsequent unbiased biological tests not only confirmed the desired function of EISA but also highlighted their emerging biological activities to control cell fate via induction of apoptosis, necroptosis, immune responses, and so on . In addition, small‐molecule‐based EISA shows good biocompatibility, easy clearance, and low immunogenicity and toxicity …”

“…Here we review the recent progress of EISA as novel nanomaterials with promising anticancer activity . In this review, we first introduce the methodology to construct EISA in biological milieu.…”

Dynamic Continuum of Molecular Assemblies for Controlling Cell Fates

“…In the past one and half decades, we have integrated the process of self‐assembly of small molecules with enzymatic reactions to manipulate the properties of supramolecular assemblies and to explore new strategies for treating human diseases . Although the formation of nanoscale assemblies by enzyme‐instructed self‐assembly (EISA) in situ (i.e., on or inside live cells) can selectively cause the death of cancer cells or profile enzyme activities, only recently, have we discovered that partial enzymatic dephosphorylation of precursors can generate dynamic and hierarchical assemblies of two components to enable cell spheroid formation . Moreover, by controlling the activity of enzymes in live cells, we were also able to control cell morphogenesis or apoptosis in a context‐dependent manner .…”