非共价键构象锁策略优化半导体聚合物纳米颗粒的 NIR-II光声/光热性能用于高效光诊疗

The development of near-infrared-II (NIR-II)-absorbing nano-agents for NIR-II photoacoustic imaging (PAI)-guided photothermal therapy (PTT) provides opportunities to advance the development of deep tissue photo-theranostics. Despite the superiority of semiconducting polymer nanoparticles (SPNs) for NIR-II PAI and PTT, their limited photoacoustic/photothermal performance makes achieving effective in vivo phototheranostics still a huge challenge. In this work, we propose a noncovalent conformational lock (NCL)-based molecular engineering strategy to improve the NIR-II photoacoustic/photothermal performance of SPNs for high-efficiency phototheranostics in vivo. The introduction of NCL is favorable to improve the backbone planarity of the semiconducting polymer to enhance the light-harvesting capability, resulting in amplified NIR-II photo-acoustic/photothermal output. By virtue of the low toxicity, suitable size, and improved photophysical properties, the optimal SPN3 not only can be efficiently internalized by 4T1 cancer cells to kill the cells under NIR-II light excitation but also light up the tumor profile via NIR-II PAI after systemic administration, which further guides the NIR-II PTT for efficient tumor ablation. Our investigation therefore provides a unique molecular design strategy to amplify the NIR-II photo-acoustic/photothermal signals of SPNs for improved in vivo phototheranostics.