Wang Hui,Tang Cui,Xiang Yuxia,Zou Chan,Hu Jianming,Yang Guoping,Zhou Wenhu
Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine’s potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.
Ning Yang,Weikun Li,Zhicheng Qian,Xin Tan,Zonghao Liu,Feiling Feng,Ling Liu,Liqin Ge
Pulmonary embolism remains the third leading cause of human mortality after malignant tumors and myocardial infarction. Commonly available thrombolytic therapeutic agents suffer from the limitations of very short half-life, inadequate targeting, limited clot penetration, and a propensity for severe bleeding. Inspired by the trident, we developed the armor-piercing microcapsule (MC), fucoidan-urokinase-S-nitrosoglutathione-polydopamine@MC (FUGP@MC), which exhibited a triple combination of photothermal, mechanical and pharmacological thrombolysis for the therapeutic treatment of acute pulmonary embolism (APE). Briefly, the outermost fucoidan layer was utilized for targeting to the APE area. Programmed APE treatment was triggered by near-infrared (NIR) light irradiation. Photothermal thrombolytic therapy was carried out by photothermal conversion of polydopamine. The photothermal conversion broke the S-nitroso bond in S-nitrosoglutathione (GSNO) and produced large amounts of nitric oxide (NO) for mechanical thrombolysis, which subsequently disrupted the interfacial structure of microcapsule to stimulate the release of the urokinase (UK), leading to a triple synergistic thrombolytic effect. The results demonstrated that the embolization residual rate of FUGP@MC (contained ≈ 1452.5 IU/kg UK) group was significantly lower than that of UK (10,000 IU/kg) group (6.35 % VS 16.78 %). Remarkably, FUGP@MC demonstrated a reliable in vivo biosafety proficiency. In summary, trident-inspired armor-piercing microcapsule FUGP@MC reveals a potential avenue for advancing pulmonary embolism therapeutics and promises to be a safer alternative candidate to current drug approaches.