Designing efficient organic near-infrared (NIR) photosensitizers (PSs) is crucial for improving tumor photodynamic therapy (PDT). However, their practical application is often limited by poor performance and incomplete understanding of inter-system cross (ISC) kinetics. This paper proposes a terminal group modulation strategy for constructing A-D-A′-D-A type near-infrared quenchers with enhanced ISC efficiency. Three π-conjugated oligomers (O1-O3) were synthesized by integrating the same D-A′-D core and different terminal receptor units. The obtained nanoparticles (ONPs 1 - ONPs 3) exhibited similar characteristics in morphology, particle size, optical absorption and emission properties. Notably, the ROS production ability of ONPs 1 was significantly superior to that of ONPs 2 and ONPs 3. Theoretical calculations revealed that the phenyl terminal group in ONPs 1 significantly enhanced the ISC efficiency (up to 28%), attributed to the reduction of the singlet-triplet energy gap (ΔEST), the decrease of oscillator strength (f), and the increase of the spin-orbit coupling (SOC) constant (λ). These properties promoted the efficient conversion of singlet (S1) excitons to triplet (T1) states, facilitating energy transfer to molecular oxygen or electron transfer to surrounding receptors, ultimately enhancing ROS production during PDT. Therefore, ONPs 1 achieved the highest ROS production capacity (6.8 times higher than indocyanine green (ICG)), and significantly increased the singlet oxygen (1O2) yield (2.2%, ICG was 0.2%). In addition, ONPs 1 was also confirmed to produce hydroxyl radicals (•OH). In summary, these advantages enabled ONPs 1 to achieve potent I-type and II-type synergistic PDT efficacy both in vitro and in vivo models. This study provides rational design guidance for the development of high-performance organic near-infrared photosensitizers, which have enhanced ISC efficiency and are used for advanced photodynamic cancer treatment. This research was published in ACS Nano under the title "Triplet π-Conjugated Oligomer Nanoparticles with High Intersystem Crossing Efficiency for 808 nm Laser-Activated Photodynamic Therapy".
References: DOI: 10.1021/acsnano.5c1879