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

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.