State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials, Ministry of Education, Frontiers Science Center for Cell Responses, and College of Life Sciences, Nankai University, Tianjin, 300071, China.
Tianjin Key Laboratory of Biomedical Materials and Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, 300192, China.
Nat Commun. 2023 Oct 28;14(1):6881. doi: 10.1038/s41467-023-42691-8.
The formation of an occlusive thrombus in the blood vessel is the main culprit for numerous life-threatening cardiovascular diseases that represent the leading cause of morbidity and mortality worldwide. Herein, we develop a polymer nanoplatform that integrates long-wavelength second near-infrared (NIR-II) photoacoustic imaging-based thrombosis detection and antithrombotic activity. We design and synthesize a semiconducting homopolymer with strong absorption in the NIR-II region and molecular motion that boosts photothermal conversion and photoacoustic signal. We dope the homopolymer with a thermosensitive nitric oxide donor to formulate a nanoplatform, on which a fibrin-specific ligand is functionalized to ensure selective thrombus targeting. We show that with strong NIR-II light harvesting capability, bright photoacoustic signal and active thrombus accumulation ability, the NIR-II photoacoustic nanoprobes are able to sensitively and selectively delineate thrombi. We find that the nanoplatform also displays rapid and efficient blood clot removal activity with nearly complete blood flow restoration in both carotid thrombosis models and low extremity arterial thrombosis models under NIR-II light trigger by integrating a thrombus-localized photothermal effect and on-demand nitric oxide release. This nanoplatform offers a versatile approach for the diagnosis and treatment of life-threatening diseases caused by various thrombotic disorders.
血管内闭塞性血栓的形成是许多危及生命的心血管疾病的主要罪魁祸首,这些疾病是全球发病率和死亡率的主要原因。在此,我们开发了一种聚合物纳米平台,该平台集成了基于长波长近红外二区(NIR-II)光声成像的血栓检测和抗血栓活性。我们设计并合成了一种在 NIR-II 区域具有强吸收且分子运动增强光热转换和光声信号的半导体均聚物。我们将该均聚物与热敏一氧化氮供体掺杂,以制定纳米平台,在该平台上功能化纤维蛋白特异性配体以确保选择性血栓靶向。我们表明,具有强近红外二区光收集能力、明亮的光声信号和活跃的血栓积累能力,NIR-II 光声纳米探针能够灵敏且选择性地描绘血栓。我们发现,该纳米平台还通过整合血栓定位光热效应和按需一氧化氮释放,在近红外二区光触发下,在颈动脉血栓模型和下肢动脉血栓模型中,具有快速高效的清除血凝块的作用,几乎完全恢复血流。该纳米平台为各种血栓性疾病引起的危及生命疾病的诊断和治疗提供了一种多功能方法。
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