Abstract
Like biomacromolecules, certain small molecules (e.g., aggregators) are able to self-assemble in the aqueous phase to form nanoscale aggregates. Though it is well-established that the aggregates may interact with enzymes in vitro, the study of the biological activities of assemblies of small molecules in the cellular environment is only at its beginning. This review summarizes the recent progress in exploring the biological functions of supramolecular assemblies of small molecules (SASMs). We first discuss the use of SASMs to inhibit pathogenic cells, such as cancer cells and bacteria. The use of SASMs to target different parts of cancer cells, such as the pericellular space, the cytosol, and subcellular organelles, and to combine with other bioactive entities (e.g., proteins and clinically used drugs), is particularly promising for addressing the challenge of acquired multidrug resistance in cancer therapy. Then, we describe the use of SASMs to sustain physiological functions of normal cells, that is, promoting cell proliferation and differentiation for tissue regeneration. After that, we show the use of SASMs as a basic tool to research cell behaviors, for instance, identifying specific cells, improving enzyme probes, revealing membrane dynamics, imaging molecular self-assembly, and mimicking context-dependent signaling. Finally, we give an outlook on the research of SASMs. We expect that this review, by highlighting the biological functions of SASMs, provides a starting point to explore the chemical biology of SASMs. Supramolecular assemblies of small molecules, exhibiting emergent properties, are becoming a new and dynamic molecular platform for biological functions and for developing novel therapeutic approaches.