A new generation of multifunctional therapeutic platforms: Coordination-driven self-assembled metallacycles

Metallacycles, typically assembled from functional pyridine ligands and metals by coordination-driven self-assembly, have emerged as a novel and highly favoured class of supramolecular macrocycles in both academia and industry. Due to their facile functionalization, reversible stimulus responses, and positively charged skeletons, metallacycles have attracted widespread attention across various fields including catalysis, sensing, optoelectronics, and biomedicine. More importantly, metallacycles can combine with organic small molecules or targeted molecules or polymers to form multifunctional metal-supramolecular assemblies, or metallacycle-based agents, through hierarchical self-assembly or postmodification. This ability makes metallacycles a revolutionary tool with unparalleled potential for both diagnosis and treatment. In this review, we summarize the synthetic strategies and functionalization methods for the construction of metallacycle assemblies with various shapes and of metallacycle-based agents. Then, we describe representative advances and discuss the current challenges in the biomedical application of metallacycles, including studies on their interactions with biomolecules, bioimaging, biosensing, drug delivery, and antibacterial and antitumor effects.