Trident-inspired fucoidan-based armor-piercing microcapsule for programmed acute pulmonary embolism treatment.

IF 5.4 2区 医学 Q1 BIOPHYSICS
Ning Yang, Weikun Li, Zhicheng Qian, Xin Tan, Zonghao Liu, Feiling Feng, Ling Liu, Liqin Ge
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Abstract

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.

基于褐藻糖胶的三叉启发穿甲微胶囊,用于急性肺栓塞的程序化治疗。
肺栓塞仍然是继恶性肿瘤和心肌梗塞之后导致人类死亡的第三大原因。常见的溶栓治疗药物存在半衰期极短、靶向性不足、血块穿透力有限以及易导致严重出血等局限性。受三叉戟的启发,我们开发了穿甲微囊(MC)--褐藻糖胶-尿激酶-S-亚硝基谷胱甘肽-多巴胺@MC(FUGP@MC),它具有光热、机械和药物溶栓三重功效,可用于急性肺栓塞(APE)的治疗。简而言之,褐藻糖胶的最外层被用于靶向 APE 区域。通过近红外线(NIR)照射触发程序化APE治疗。光热溶栓疗法是通过多巴胺的光热转换来实现的。光热转换破坏了 S-亚硝基谷胱甘肽(GSNO)中的 S-亚硝基键,产生了大量的一氧化氮(NO)用于机械溶栓,随后破坏了微囊的界面结构,刺激了尿激酶(UK)的释放,从而产生了三重协同溶栓效应。结果表明,FUGP@MC(含≈1452.5 IU/kg UK)组的栓塞残留率明显低于UK(10,000 IU/kg)组(6.35 % VS 16.78 %)。值得注意的是,FUGP@MC 在体内表现出了可靠的生物安全性。总之,受三叉戟启发的穿甲微囊 FUGP@MC 为肺栓塞疗法的发展提供了一条潜在的途径,有望成为当前药物疗法的一种更安全的替代选择。
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来源期刊
Colloids and Surfaces B: Biointerfaces
Colloids and Surfaces B: Biointerfaces 生物-材料科学:生物材料
CiteScore
11.10
自引率
3.40%
发文量
730
审稿时长
42 days
期刊介绍: Colloids and Surfaces B: Biointerfaces is an international journal devoted to fundamental and applied research on colloid and interfacial phenomena in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical, biotechnological, food and cosmetic fields. Submissions that: (1) deal solely with biological phenomena and do not describe the physico-chemical or colloid-chemical background and/or mechanism of the phenomena, and (2) deal solely with colloid/interfacial phenomena and do not have appropriate biological content or relevance, are outside the scope of the journal and will not be considered for publication. The journal publishes regular research papers, reviews, short communications and invited perspective articles, called BioInterface Perspectives. The BioInterface Perspective provide researchers the opportunity to review their own work, as well as provide insight into the work of others that inspired and influenced the author. Regular articles should have a maximum total length of 6,000 words. In addition, a (combined) maximum of 8 normal-sized figures and/or tables is allowed (so for instance 3 tables and 5 figures). For multiple-panel figures each set of two panels equates to one figure. Short communications should not exceed half of the above. It is required to give on the article cover page a short statistical summary of the article listing the total number of words and tables/figures.
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