“Click” cycloadditions offer effective pathways for the modifications of supramolecular structures, polymers, and nanomaterials. These reactions include bioorthogonal mechanisms that do not interfere with the biological processes, providing a type of chemistry to operate directly in living environments, such as cells and animals. As a result, the “click” cycloadditions represent highly and selective tools for tailoring the properties of nanomedicine scaffolds, expanding the efficacy of multiple therapeutic strategies. We focused this minireview on the bioorthogonal cycloadditions, presenting an insight into the strategies to modify nanostructured biomedical scaffolds inside living systems. We organized the contributions according to the three main mechanisms of “click” cycloadditions: strain-promoted sydnone-alkyne, tetrazine ligation, and strain-promoted [3+2] azido-alkyne.
