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.

用于 NIR-II 光声成像 (PAI) 引导光热治疗 (PTT) 的近红外 II (NIR-II) 吸收纳米制剂的开发为推进深部组织光治疗学的发展提供了机会。尽管半导体聚合物纳米颗粒（SPN）在 NIR-II PAI 和 PTT 方面具有优越性，但其有限的光声/光热性能使得实现有效的体内光治疗仍然是一个巨大的挑战。在这项工作中，我们提出了一种基于非共价构象锁（NCL）的分子工程策略，以提高 SPN 的 NIR-II 光声/光热性能，以实现体内高效光治疗。NCL的引入有利于改善半导体聚合物主链的平面度，从而增强光捕获能力，从而增强NIR-II光声/光热输出。凭借低毒性、合适的尺寸和改进的光物理特性，最佳的SPN3不仅可以被4T1癌细胞有效内化，在NIR-II光激发下杀死细胞，而且可以通过NIR-II PAI照亮肿瘤轮廓全身给药后，进一步指导 NIR-II PTT 进行有效的肿瘤消融。因此，我们的研究提供了一种独特的分子设计策略来放大 SPN 的 NIR-II 光声/光热信号，从而改善体内光治疗学。