Semiconducting Polymers Containing Benzobisthiadiazole Based on Donor Conjugation Extension Strategy Enabling NIR-II Photoacoustic Imaging Performance Improvement

Semiconducting polymer contrast-agent-based photoacoustic (PA) imaging technology within the second near-infrared (NIR-II) window possesses unique advantages. While the lack of effective molecular design strategies has resulted in a distinct gap between the signal intensity of these materials and the requirements of clinical applications. It is therefore of significant practical importance to clarify the design rules of D−π–A type polymers and enhance the PA imaging performance of polymer-based NIR-II contrast agents. In this study, a series of NIR-II polymers (PT-BBT, PTT-BBT, and PDTT-BBT) were designed and synthesized by copolymerizing the classic benzo[1,2-c:4,5-c’]bis([1,2,5]thiadiazole) (BBT) acceptor (A) with donor (D) units containing varying numbers of thiophene units (T, TT, and DTT), and the impact of effective conjugation extension of D units in D−π–A polymers on PA imaging performance was comprehensively studied. The time-dependent density functional theory (TD-DFT) computational results indicated that an increase in the number of thiophene units in the D unit was associated with an increase in the dihedral angle of D−π–A polymers. In vitro PA characterization demonstrated that under identical concentration conditions, PDTT-BBT@NPs exhibited the most optimal NIR-II PA signal of the three (with a signal-to-noise ratio reaching 182.5). In vivo PA imaging based on PDTT-BBT@NPs demonstrated the capacity to identify ear microvessels down to 50 μm and brain vessels down to 100 μm. These findings suggest that increasing the conjugation length of the D unit in D−π–A polymers is an effective strategy to enhance the performance of NIR-II PA imaging.