Donor Planarity‐Induced Molecular Twist in Donor‐Acceptor‐Donor AIEgens for Efficient NIR‐II Fluorescence and Photothermal Therapy

Abstract Aggregation‐induced emission (AIE) active donor‐acceptor‐donor (D‐A‐D) small molecules represent promising candidates for second near‐infrared fluorescence imaging (NIR‐II FLI) guided photothermal therapy (PTT) in anti‐tumor applications. Trianiline and tetraphenylvinyl analogues are often used as electron donors, but may have limitations, such as moderate electron donor capabilities or suboptimal AIE properties. Herein, a molecular design strategy integrating π‐conjugated planar electron donors are reported within a structurally twisted D‐A‐D framework to develop improved AIE‐type NIR‐II probes. Among the synthesized molecules, BBT‐TIT, which incorporates the electron‐rich TIT donor, simultaneously exhibits a high molar extinction coefficient (ɛ = 2.352 × 10⁴ M⁻¹ cm⁻¹) and significant aggregation‐induced emission behavior (αAIE = 4.5). Notably, when formulated into water‐soluble nanoparticles (BBT‐TIT NPs), these particles demonstrated bright NIR‐II fluorescence (FL) peaking at 1068 nm (QY = 1.85% in water) and efficient photothermal conversion (PCE η = 53.44%). In vivo, studies have successfully demonstrated the application of NPs in high‐contrast NIR‐II FL angiography and tumor imaging in living mice, as well as effective photothermal properties leading to significant tumor ablation. This study shows that combining selected planar electron donors with a twisted D‐A‐D architecture promises great potential for developing advanced AIE‐active agents in NIR‐II fluorescence imaging‐guided photothermal therapy.