Design of One-For-All Near-Infrared Aggregation-Induced Emission Nanoaggregates for Boosting Theranostic Efficacy

Fluorescence-guided phototherapy with integrated diagnostic and therapeutic functions has great potential in the field of precision medicine, as they fully utilize light for energy conversion or transduction, and have the advantages of multifunctionality, low cost, and convenient. From a diagnostic perspective, near-infrared fluorescence imaging (FLI) has lower interference from autofluorescence, improved imaging depth, and higher sensitivity compared to conventional imaging in the visible light region. On the other hand, photothermal therapy (PTT) and photodynamic therapy (PDT) have received great research attention due to their non-invasive, controllable, and low drug resistance characteristics. PTT uses non-radiative transitions of excited molecular states to convert light energy into heat for therapy, while PDT involves energy transfer processes of excited state molecules, producing highly reactive oxygen species, inducing cell damage and apoptosis. Combining PTT and PDT with fluorescence localization of lesions could lead to better diagnostic and therapeutic effects. However, the competitive energy relaxation pathways of molecules are difficult to regulate, and the fluorescence of many planar organic molecules is quenched upon aggregation, making it difficult to achieve efficient FLI, PTT, and PDT simultaneously. Aggregate science offers more opportunities to solve this problem, as the energy dissipation pathways of aggregates are more diverse, providing more possibilities for constructing "one-for-all" phototheranostic agents and realizing their multifunctionality. Based on this, this study reports a multifunctional diagnostic and therapeutic platform with near-infrared emission, high fluorescence quantum yield, reactive oxygen species generation efficiency, and photothermal conversion efficiency. <i>In vivo</i> studies show that the use of aggregation-induced emission (AIE) nanoaggregates in this platform can make mouse tumors show bright fluorescence, while exhibiting good photodynamic and photothermal therapy effects, ultimately completely eliminating the tumors. This study is of great significance for the rational design and synthesis of multifunctional near-infrared nanoaggregates with high energy dissipation utilization efficiency for precise diagnosis and effective treatment of tumors.