Molecularly self‐fueled nano-penetrator for nonpharmaceutical treatment of thrombosis and ischemic stroke

Hongyuan Zhang, Zhiqiang Zhao, Shengnan Sun, Sen Zhang, Yuequan Wang, Xuanbo Zhang, Jin Sun, Zhonggui He, Shenwu Zhang () and Cong Luo ()
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Hongyuan Zhang: Shenyang Pharmaceutical University
Zhiqiang Zhao: Shenyang Pharmaceutical University
Shengnan Sun: Shenyang Pharmaceutical University
Sen Zhang: Shenyang Pharmaceutical University
Yuequan Wang: Shenyang Pharmaceutical University
Xuanbo Zhang: Shenyang Pharmaceutical University
Jin Sun: Shenyang Pharmaceutical University
Zhonggui He: Shenyang Pharmaceutical University
Shenwu Zhang: Shenyang Pharmaceutical University
Cong Luo: Shenyang Pharmaceutical University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Thrombotic cerebro-cardiovascular diseases are the leading causes of disability and death worldwide. However, current drug therapeutics are compromised by narrow therapeutic windows, unsatisfactory thrombolysis effects, severe bleeding events, and high recurrence rates. In this study, we exploit a self-propelling nano-penetrator with high fuel loading and controllable motion features, which is molecularly co-assembled using a photothermal photosensitizer (DiR) and a photothermal-activable NO donor (BNN6). The precisely engineered nano-penetrator of the BNN6-DiR fuel pair shows distinct advantages in terms of NO productivity and autonomous motion under laser irradiation. In animal models of artery/vein thrombosis and acute ischemic stroke, the self‐fueled nano-penetrator enables self-navigated thrombus-homing accumulation, self-propelled clot deep penetration, fluorescence image-guided photothermal/mechanical thrombolysis, and NO-mediated prevention of thrombosis recurrence and acute ischemic stroke salvage. As expected, the molecularly self-fueled nano-penetrator displayed favorable therapeutic outcomes without bleeding risk compared to the clinically available thrombolytic drug. This study offers a facile, safe, and effective nonpharmaceutical modality towards the clinical treatment of thrombosis and ischemic stroke.

Date: 2023
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DOI: 10.1038/s41467-023-35895-5

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