Finding the Sweet Spot: Isomerization Strategy Enables Balanced Energy Dissipation of NIR-II AIEgens for “One-for-All” Tumor Phototheranostics

Abstract “One-for-all” phototheranostics with the second near-infrared window (NIR-II) emission have garnered great enthusiasm for seamlessly integrating superb imaging and high-efficiency therapy into a single formula. However, it is still a nontrivial conundrum to achieve balanced excited-state energy dissipation to guarantee high NIR-II brightness, photothermal conversion, and reactive oxygen species (ROS) generation. As a powerful tool for balancing radiative and nonradiative decays, aggregation-induced emission luminogens (AIEgens) are emerging as a promising frontier in developing “one-for-all” phototheranostic agents, while their phototheranostic performance needs to be further improved. In this contribution, we designed and synthesized two positional isomers, 5BT-PBPT and 6BT-PBPT, by attaching donors at the 5- and 6-positions of the benzo[b]thiophene (BT) segment, respectively, to investigate the effect of positional isomerism on the phototheranostic performance of NIR-II AIEgens. Interestingly, both experimental and computational results demonstrate that the isomerization affords great strength in tuning energy levels, structural conformations, aggregation behaviors, and excited-state energy dissipation. Consequently, a sweet spot for fully utilizing excitation energy was achieved in 5BT-PBPT nanoparticles (NPs), which exhibited not only strong NIR absorption but also high NIR-II fluorescence brightness, strong ROS production, and excellent photothermal conversion efficiency (η). Benefiting from this, 5BT-PBPT NPs afforded superior performance in the “one-for-all” phototheranostics for orthotopic breast tumor treatment. This study fully demonstrates the effectiveness of the isomeric engineering strategy in comprehensively improving the phototheranostic capabilities of NIR-II AIEgens and thereby provides an effective approach for the construction of high-performance NIR-II “one-for-all” phototheranostic agents.