Supramolecular dyes: advancing precision medicine through molecular engineering

Precision medicine is aimed at achieving a more personalized approach tailored to individual characteristics and urgently requires the development of precise diagnostic and therapeutic methods. Small-molecule dyes play indispensable roles in medical imaging and surgery procedures, attracting significant attention regarding disease diagnosis and therapy. However, their widespread utilization for accurate tumor localization and long-term intraoperative imaging remains hindered by their inherent limitations, including tedious synthesis protocols, poor photostability, susceptibility to fluorescence quenching in physiological environments, and rapid systemic clearance. Supramolecular dyes, defined as small-molecule dye-based assemblies, usually present unique and superior photophysical properties, including tunable optical properties, enhanced photodynamic and photothermal performance, improved photostability and optimized anti-quenching capability, collectively enabling high-precision optical diagnosis and therapy. Despite remarkable progress in supramolecular dyes, a systemic review summarizing their applications in precision biomedicine remains lacking. In this review, we systematically summarize the recent advances on the development of supramolecular dyes across three key self-assembly systems: supramolecular coordination complexes (SCCs) systems, host-guest systems (including cyclodextrin, cucurbit[n]urils (CB [n]s), calixarenes and pillararenes), and enzyme instructed self-assembly (EISA) systems. Moreover, we highlight current challenges and future perspectives to accelerate their translation from fundamental research to clinical applications.