Elaborately Engineering a Self-Indicating Dual-Drug Nanoassembly for Site-Specific Photothermal-Potentiated Thrombus Penetration and Thrombolysis.

Abstract

Thrombotic cardio-cerebrovascular diseases seriously threaten human health. Currently, conventional thrombolytic treatments are challenged by the low utilization, inferior thrombus penetration, and high off-target bleeding risks of most thrombolytic drugs, resulting in unsatisfactory treatment outcomes. Herein, it is proposed that these challenges can be overcome by precisely integrating the conventional thrombolytic strategy with photothermal therapy. After co-assembly engineering optimization, a fibrin-targeting peptide-decorated nanoassembly of DiR (a photothermal probe) and ticagrelor (TGL, an antiplatelet drug) is prepared for thrombus-homing delivery, abbreviated as FT-DT NPs. The elaborately engineered nanoassembly shows multiple advantages, including simple preparation with high drug co-loading capacity, synchronous delivery of two drugs with long systemic circulation, thrombus-targeted accumulation with self-indicating function, as well as photothermal-potentiated thrombus penetration and thrombolysis with high therapeutic efficacy. As expected, FT-DT NPs not only show bright fluorescence signals in the embolized vessels, but also perform photothermal/antiplatelet synergistic thrombolysis in vivo. This study offers a simple and versatile co-delivery nanoplatform for imaging-guided photothermal/antiplatelet dual-modality thrombolysis.

• Authors: Zhiqiang Zhao, Xuanbo Zhang, Hongyuan Zhang, Xinzhu Shan, Meiyu Bai, Zhe Wang, Fujun Yang, Haotian Zhang, Qiming Kan, Bingjun Sun, Jin Sun, Zhonggui He, Cong Luo
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 4 Pg. e2104264 (02 2022) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34802198 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• Fibrinolytic Agents
• Platelet Aggregation Inhibitors
• Ticagrelor

Topics

• Animals
• Disease Models, Animal
• Drug Delivery Systems
• Fibrinolytic Agents (administration & dosage, therapeutic use)
• Mice
• Nanoparticles
• Photothermal Therapy (methods)
• Platelet Aggregation Inhibitors (administration & dosage, therapeutic use)
• Rats
• Thrombolytic Therapy (methods)
• Thrombosis (therapy)
• Ticagrelor (administration & dosage, therapeutic use)