Reprogramming tumor-associated macrophages to an antitumor M1 phenotype by photodynamic therapyi s ap romising strategy to overcome the immunosuppression of tumor microenvironment for boosted immunotherapy. However,itremains unclear howthe reactive oxygen species (ROS) generated from type Ia nd II mechanisms,r elate to the macrophage polarization efficacy.H erein, we design and synthesize three donor-acceptor structured photosensitizers with varied ROS-generating efficiencies.S urprisingly,w e discovered that the extracellular ROS generated from type I mechanism are mainly responsible for reprogramming the macrophages from ap ro-tumor type (M2) to an anti-tumor state (M1). In vivo experiments prove that the photosensitizer can trigger photodynamic immunotherapyf or effective suppression of the tumor growth, while the therapeutic outcome is abolished with depleted macrophages.O verall, our strategy highlights the designing guideline of macrophage-activatable photosensitizers.

It remains highly challenging to identify small molecule‐based photothermal agents with a high photothermal conversion efficiency (PTCE). Herein, we adopt a double bond‐based molecular motor concept to develop a new class of small photothermal agents to break the current design bottleneck. As the double‐bond is twisted by strong twisted intramolecular charge transfer (TICT) upon irradiation, the excited agents can deactivate non‐radiatively through the conical intersection (CI) of internal conversion, which is called photoinduced nonadiabatic decay. Such agents possess a high PTCE of 90.0 %, facilitating low‐temperature photothermal therapy in the presence of a heat shock protein 70 inhibitor. In addition, the behavior and mechanism of NIR laser‐triggered molecular motions for generating heat through the CI pathway have been further understood through theoretical and experimental evidence, providing a design principle for highly efficient photothermal and photoacoustic agents.

Photoacoustic agents have been of vital importance for improvingthe imaging contrast and reliability against selfinterference from endogenous substances.H erein, we synthesized as eries of thiadiazoloquinoxaline (TQ)-based semiconducting polymers (SPs) with ab road absorption covering from NIR-I to NIR-II regions.A mong them, the excited s-BDT-TQE, ar epeating unit of SPs,s hows al arge dihedral angle and narrowa diabatic energy as well as low radiative decay, attributing to its strongly electron-deficient ester-substituted TQ-segment. In addition, its more vigorous molecular motions trigger ah igher reorganization energy that further yields an efficient photoinduced nonradiative decay, which has been carefully examined and understood by theoretical calculation. Thus,B DT-TQE SP-cored nanoparticles with twisted intramolecular charge transfer (TICT) feature exhibit ah igh NIR-II photothermal conversion efficiency (61.6 %) and preferable PA tracking of in situ hepatic tumor growth for more than 20 days.This study highlights aunique strategy for constructing efficient NIR-II photoacoustic agents via TICTenhanced PNRD effect, advancing their applications for in vivo bioimaging.

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Planar luminogens have encountered difficulties in overcoming intrinsic aggregation‐caused emission quenching by intermolecular π‐π stacking interactions. Although excited‐state double‐bond reorganization (ESDBR) can guide us on designing planar aggregation‐induced emission (AIE) luminogens (AIEgens), its mechanism has yet been elucidated. Major challenges in the field include methods to efficiently restrict ESDBR and enhance AIE performance without using bulky substituents (e.g., tetraphenylethylene and triphenylamine). In this study, we rationally developed fluoro‐substituent AIEgens with stronger intermolecular H‐bonding interaction for restricted molecular motions and increased crystal density, leading to decreased nonradiative decay rate by one order of magnitude. The adjusted ESDBR properties also show a corresponding response to variation in viscosity. Furthermore, their aggregation‐induced reactive oxygen species (ROS) generations have been discovered. The application of such planar AIEgen in treating multidrug‐resistant bacteria has been demonstrated in a mouse model. The relationship between ROS generation and distinct E/Z‐configurational stacking behaviors have been further understood, providing a design principle for synthesizing planar AIEgen‐based photosensitizers.