Isomer Engineering of NIR‐II Aggregation‐Induced Emission for the Theranostics of MRSA‐Induced Abscess

ABSTRACT The escalating crisis of antimicrobial resistance poses an urgent threat to global public health. Conventional photodynamic therapy (PDT) is limited by oxygen dependence and restricted light penetration, which can compromise its therapeutic efficacy in the hypoxic microenvironment of deep abscesses. Herein, we report a positional isomer engineering strategy that transforms a thioxanthene (THX) scaffold into aggregation‐induced emission luminogens (AIEgens) with fluorescence extending into the second near‐infrared (NIR‐II) window and dual‐modal therapeutic capability. Theoretical and photophysical studies revealed that the para‐configured isomer (Ph‐p‐THX) exhibited a smaller energy gap and higher oscillator strength than its meta‐counterpart (Ph‐m‐THX). These electronic features provide more favorable singlet‐triplet energy alignment, thereby supporting triplet‐involved Type‐I‐dominant mixed reactive oxygen species (ROS) generation under hypoxic‐relevant conditions associated with abscess microenvironments. In parallel, the narrowed energy gap and enhanced light‐harvesting capability contribute to efficient photothermal conversion. As a result, Ph‐p‐THX enabled NIR‐II imaging‐guided treatment and exhibited superior antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) abscesses in vivo. Overall, this study highlights positional isomerization as an effective strategy for optimizing THX‐based AIE photosensitizers for antimicrobial theranostic applications.