Graduate Institute of Biomedical Materials and Tissue Engineering, International Ph.D. Program in Biomedical Engineering, Graduate Institute of Nanomedicine and Medical Engineering, College of Biomedical Engineering, Taipei Medical University, New Taipei City, 23561, Taiwan.
Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.
J Nanobiotechnology. 2024 Aug 8;22(1):470. doi: 10.1186/s12951-024-02716-w.
Thrombotic cardiovascular diseases are a prevalent factor contributing to both physical impairment and mortality. Thrombolysis and ischemic mitigation have emerged as leading contemporary therapeutic approaches for addressing the consequences of ischemic injury and reperfusion damage. Herein, an innovative cellular-cloaked spermatozoon-driven microcellular submarine (SPCS), comprised of multimodal motifs, was designed to integrate nano-assembly thrombolytics with an immunomodulatory ability derived from innate magnetic hyperthermia. Rheotaxis-based navigation was utilized to home to and cross the clot barrier, and finally accumulate in ischemic vascular organs, where the thrombolytic motif was "switched-on" by the action of thrombus magnetic red blood cell-driven magnetic hyperthermia. In a murine model, the SPCS system combining innate magnetic hyperthermia demonstrated the capacity to augment delivery efficacy, produce nanotherapeutic outcomes, exhibit potent thrombolytic activity, and ameliorate ischemic tissue damage. These findings underscore the multifaceted potential of our designed approach, offering both thrombolytic and ischemia-mitigating effects. Given its extended therapeutic effects and thrombus-targeting capability, this biocompatible SPCS system holds promise as an innovative therapeutic agent for enhancing efficacy and preventing risks after managing thrombosis.
血栓性心血管疾病是导致身体损伤和死亡的一个普遍因素。溶栓和缺血缓解已成为解决缺血性损伤和再灌注损伤后果的主要当代治疗方法。在此，设计了一种由多模式基元组成的创新细胞伪装的精子驱动的微型潜艇（SPCS），将纳米组装溶栓剂与源自固有磁热疗的免疫调节能力结合在一起。基于切向流的导航用于归巢和穿越血栓屏障，最后在缺血性血管器官中积累，其中溶栓基元通过血栓磁红细胞驱动的磁热疗的作用“开启”。在小鼠模型中，结合固有磁热疗的 SPCS 系统表现出增强递送功效、产生纳米治疗效果、表现出强大的溶栓活性和改善缺血组织损伤的能力。这些发现突显了我们设计方法的多方面潜力，提供了溶栓和缺血缓解作用。鉴于其延长的治疗效果和血栓靶向能力，这种生物相容性的 SPCS 系统有望成为一种创新的治疗剂，可在管理血栓后提高疗效并预防风险。
