Macrocyclic‐Engineered Supramolecular AIE Photosensitizer for Boosted NIR‐II Phototheranostics

Multimodal phototheranostics on the basis of second near‐infrared (NIR‐II) aggregation‐induced emission (AIE) small molecules has emerged as a promising paradigm for cancer treatment. Nevertheless, beyond molecular design, precise control over aggregation behavior that is critical for tuning optical properties and therapeutic functions, remains challenging. Herein, we report a supramolecular aggregate‐engineering strategy that employs pillar[5]arene‐mediated host–guest complexation to direct the assembly of NIR‐II AIE luminogens. By finely balancing excited state energy dissipation pathways, the resulting supramolecular AIE nanoparticles (PTNI NPs) achieve significantly enhanced performance in multimodal NIR‐II fluorescence imaging (FLI)‐guided synergistic photodynamic and photothermal therapy of orthotopic 4T1 breast tumors, outperforming their macrocycle‐free counterpart. In vivo studies demonstrated that PTNI NPs exhibited prolonged tumor retention and intense NIR‐II fluorescence, leading to pronounced tumor growth inhibition and enabling precise fluorescence‐guided surgical navigation. This supramolecular assembly approach offers a generalizable route to advanced phototheranostic agents with tailored optical and therapeutic outputs.