Recent advances in targeting cyanine dyes: hierarchical targeting mechanisms and theranostic integration for multi-disease precision therapy.

The development of novel theranostic agents is a key initiative to address current limitations in disease diagnosis and therapy. Notably, targeting cyanine dyes (TCDs), by virtue of their excellent optical imaging performance, versatile structural modifiability, and multi-dimensional targeting specificity, facilitate the directional recognition of disease regions and exhibit tremendous application potential in theranostics. While a variety of TCDs have been successfully developed and their theranostic efficacy experimentally validated, researchers still lack a systematic summary of related studies. Although related advances in fluorescent probes, tumor theranostics, and NIR-II fluorophores have been reviewed, a focused and systematic overview of TCDs in terms of their synthesis, hierarchical targeting mechanisms, and multi-disease theranostic applications remains limited. Accordingly, this article systematically reviews TCDs' synthesis strategies, elucidates their "tissue-cell-organelle" hierarchical targeting mechanism, and summarizes the therapeutic applications in diseases including tumors, fibrotic diseases, metabolic diseases, and radiation-induced injuries. Compared with previous reviews, this review highlights the structure-inherent targeting properties of TCDs, their hierarchical targeting mechanisms, and their emerging theranostic potential beyond oncology. Meanwhile, this article outlines the core advantages and current challenges of TCDs in theranostic integration, and delineates key future directions, including precise and intelligent molecular design, photostability limitations, systematic preclinical evaluation, multimodal technology integration, and the expansion of disease application scenarios. It aims to provide comprehensive theoretical support for advancing the fundamental research and clinical translation of TCDs.