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Noncovalent conformational lock-based molecular engineering improves NIR-II photoacoustic/photothermal performance of semiconducting polymer nanoparticles for efficient phototheranostics

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

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Abstract

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.

摘要

开发近红外二区(NIR-II)响应的纳米制剂用于NIR-II光声成像 (PAI)引导的光热治疗(PTT)为推进深层组织光诊疗的发展提供了机遇. 尽管半导体聚合物纳米颗粒(SPNs)在NIR-II PAI和PTT中展现出巨大 的应用潜力, 但其有限的光声/光热效能使得实现高效的体内光诊疗仍 然是一个巨大的挑战. 本工作中, 我们提出了一种基于非共价键构象锁 (NCL)的分子工程策略来优化SPN的NIR-II光声/光热性能, 以实现高效 的体内光诊疗. NCL的引入有助于改善半导体聚合物主链的平面性, 增 强其捕光能力, 从而提高NIR-II光声/光热信号的输出. 优化出的SPN3 毒性低、尺寸合适、光物理性能好, 不仅能被4T1癌细胞有效摄取并在 NIR-II光激发下杀死细胞, 而且经全身给药后可通过NIR-II PAI点亮肿 瘤轮廓, 进一步指导NIR-II PTT的进行以实现高效的肿瘤热消融. 因此 本文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, 最终实现活体高效光诊疗.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (62005127), the Natural Science Foundation of Jiangsu Province (BK20200751), the Project of Jiangsu Specially-Appointed Professor (RK030STP22003), the Research Startup Fund of Nanjing University of Posts and Telecommunications (NY220068), and the Project of State Key Laboratory of Organic Electronics and Information Displays (ZS030ZR22014).

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Authors

Contributions

Author contributions Fan Q and Yin C designed the project; Yin C wrote the manuscript; Chen Ying guided the biological experiments; Chen Yang and Yang G carried out the experiments; Li P conducted the theoretical calculation; Yin L and Chen L conducted the data analysis; Liu Y and Liang X were responsible for data checking. All authors contributed to the general discussion.

Corresponding authors

Correspondence to Ying Chen  (陈莹), Chao Yin  (尹超) or Quli Fan  (范曲立).

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Conflict of interest The authors declare that they have no conflict of interest.

Additional information

Supplementary information Experimental details and supporting data are available in the online version of the paper.

Yang Chen is currently studying for his Master’s degree at Nanjing University of Posts and Telecommunications under the supervision of Professor Chao Yin. His main research interest is semiconducting nanoprobe-assisted photoacoustic imaging and photothermal therapy.

Chao Yin received his PhD degree from the Institute of Advanced Materials, Nanjing University of Posts and Telecommunications. After graduation, he moved to Chinese University of Hong Kong for postdoctoral research. Currently, he is a professor at Nanjing University of Posts and Telecommunications. His research is focused on the design and synthesis of multifunctional nanoma-terials based on organic semiconducting polymers/oligo-mers for biomedical applications.

Quli Fan is currently a professor at Nanjing University of Posts and Telecommunications, China. He received his BS and MS degrees from Nanjing University in 1996 and 1999, respectively. He obtained his PhD degree from the National University of Singapore in 2003. His research interest focuses on the development of smart and multi-functional NIR optical platform for understanding, detection, and treatment of life-threatening diseases.

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Noncovalent conformational lock-based molecular engineering improves NIR-II photoacoustic/photothermal performance of semiconducting polymer nanoparticles for efficient phototheranostics

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Chen, Y., Yang, G., Li, P. et al. Noncovalent conformational lock-based molecular engineering improves NIR-II photoacoustic/photothermal performance of semiconducting polymer nanoparticles for efficient phototheranostics. Sci. China Mater. 66, 4865–4874 (2023). https://doi.org/10.1007/s40843-023-2603-6

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