Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China; School of Pharmacy, Chengdu University, Chengdu, 610106, China.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Acta Biomater. 2023 Mar 1;158:769-781. doi: 10.1016/j.actbio.2022.12.026. Epub 2022 Dec 21.
Pathological coagulation within an injured artery and the subsequent cardiovascular complications, such as stroke and heart attack, greatly threaten human life. Inspired by the biochemical features of acute arterial thrombosis, such as abundant activated platelets and hydrogen peroxide (HO), we constructed platelet-targeted theranostic nanoparticles (CyBA/PFM NPs) with HO-triggered photoacoustic contrast enhancement and antithrombotic capabilities. CyBA/PFM NPs were designed to target platelet-rich clots via fucoidan segment within the carrier, which could be activated by HO to produce fluorescent "CyOH" molecules, thus turning on the photoacoustic signal. CyBA/PFM NPs showed obvious amplification of fluorescence following incubation with fresh clots, exhibiting efficient scavenging ability of intracellular reactive oxygen species (ROS). In a FeCl-induced mouse model of carotid thrombosis, CyBA/PFM NPs significantly amplified the photoacoustic contrast in thrombogenic tissues, effectively eliminated ROS within the occlusion site, and suppressed the thrombus formation, accompanied by a normalization of the soluble CD40L level. Given their accurate imaging potential, potent antithrombotic activities and acceptable biosafety, CyBA/PFM NPs hold strong potential as nanoscale theranostics for HO-correlated cardiovascular diseases. STATEMENT OF SIGNIFICANCE: In this study, we developed a platelet-targeted and HO-triggered nanosystem self-assembled from phenylboronated fucoidan/maltodextrin polymers and responsive near-infrared probes. The fucoidan segment within the carrier could facilitate the specific delivery of the therapeutic polymers and probes to the platelet-rich arterial thrombus. In a mouse model of FeCl-induced arterial thrombosis, the system could be activated by HO to produce fluorescent "CyOH" molecules, thus turning on the photoacoustic signal and specifically imaging thrombosed tissues. Besides, CyBA/PFM NPs significantly effectively eliminated ROS within the occlusion site and suppressed the thrombus formation. Given their theranostic potential and acceptable biosafety, this system has great potential for HO-correlated cardiovascular diseases.
损伤动脉内的病理性凝血以及随后的心血管并发症，如中风和心脏病发作，极大地威胁着人类的生命。受急性动脉血栓形成的生化特征的启发，如丰富的活化血小板和过氧化氢 (HO)，我们构建了具有 HO 触发光声对比增强和抗血栓能力的血小板靶向治疗纳米颗粒 (CyBA/PFM NPs)。CyBA/PFM NPs 被设计通过载体中的褐藻糖胶片段靶向富含血小板的血栓，该片段可被 HO 激活以产生荧光“CyOH”分子，从而开启光声信号。CyBA/PFM NPs 在与新鲜血栓孵育后显示出明显的荧光放大，表现出对细胞内活性氧物种 (ROS) 的有效清除能力。在 FeCl 诱导的颈动脉血栓形成小鼠模型中，CyBA/PFM NPs 显著放大了血栓组织中的光声对比，有效消除了闭塞部位的 ROS，并抑制了血栓形成，同时使可溶性 CD40L 水平正常化。鉴于其准确的成像潜力、强大的抗血栓活性和可接受的生物安全性，CyBA/PFM NPs 作为与 HO 相关的心血管疾病的纳米级治疗学具有很大的潜力。
在这项研究中，我们开发了一种由苯硼酸化褐藻糖胶/麦芽糊精聚合物和响应性近红外探针自组装而成的血小板靶向和 HO 触发纳米系统。载体中的褐藻糖胶片段有助于将治疗聚合物和探针特异性递送至富含血小板的动脉血栓。在 FeCl 诱导的动脉血栓形成小鼠模型中，该系统可被 HO 激活产生荧光“CyOH”分子，从而开启光声信号并特异性成像血栓组织。此外，CyBA/PFM NPs 可显著有效消除闭塞部位的 ROS 并抑制血栓形成。鉴于其治疗学潜力和可接受的生物安全性，该系统在与 HO 相关的心血管疾病方面具有巨大的潜力。
