用于血栓形成致动抗凝的肝素肽纳米颗粒,Small

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用于血栓形成致动抗凝的肝素肽纳米颗粒
Small ( IF 13.0 ) Pub Date : 2022-10-03 , DOI: 10.1002/smll.202203751
Atip Lawanprasert ₁ , Sopida Pimcharoen ₁ , Sarah E Sumner ₂ , Connor T Watson ₁ , Keefe B Manning ₁ , Girish S Kirimanjeswara _{2,

3,

4} , Scott H Medina _{1,

5}

Affiliation

尽管将近一个世纪的临床用作血液稀释剂，肝素的快速血清清除和诱发严重出血事件的可能性继续促使开发更有效的控制递送策略。稳定地将抗凝血剂释放到循环中的皮下贮库代表了一种有前途的方法，可以减少过量用药频率，维持血浆中肝素的治疗浓度，并以安全有效的方式延长抗凝血活性。据报道，皮下可递送的肝素肽纳米颗粒可在循环系统中实现持久的肝素生物利用度，同时能够按需激活肝素在血栓微环境中的抗凝作用。生物物理学研究表明，这种反应行为是由于肝素在自组装肽纳米纤维中的螯合及其机械驱动的解偶联以在凝血部位引起抗血栓形成作用。体内研究表明，这些独特的特性会聚在一起，使皮下纳米颗粒储库能够将肝素血清浓度延长一个数量级，比标准给药方案长一个数量级，同时能够延长和控制抗凝血活性。这种生物混合递送系统展示了一个潜在的可扩展平台，用于开发更安全、更易于管理和更有效的抗血栓纳米技术。体内研究表明，这些独特的特性会聚在一起，使皮下纳米颗粒储库能够将肝素血清浓度延长一个数量级，比标准给药方案长一个数量级，同时能够延长和控制抗凝血活性。这种生物混合递送系统展示了一个潜在的可扩展平台，用于开发更安全、更易于管理和更有效的抗血栓纳米技术。体内研究表明，这些独特的特性会聚在一起，使皮下纳米颗粒储库能够将肝素血清浓度延长一个数量级，比标准给药方案长一个数量级，同时能够延长和控制抗凝血活性。这种生物混合递送系统展示了一个潜在的可扩展平台，用于开发更安全、更易于管理和更有效的抗血栓纳米技术。

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Heparin-Peptide Nanogranules for Thrombosis-Actuated Anticoagulation

Despite nearly a century of clinical use as a blood thinner, heparin's rapid serum clearance and potential to induce severe bleeding events continue to urge the development of more effective controlled delivery strategies. Subcutaneous depots that steadily release the anticoagulant into circulation represent a promising approach to reducing overdose frequency, sustaining therapeutic concentrations of heparin in plasma, and prolonging anticoagulant activity in a safe and effective manner. Subcutaneously deliverable heparin-peptide nanogranules that allow for long-lasting heparin bioavailability in the circulatory system, while enabling on-demand activation of heparin's anticoagulant effects in the thrombus microenvironment, are reported. Biophysical studies demonstrate this responsive behavior is due to the sequestration of heparin within self-assembling peptide nanofibrils and its mechanically actuated decoupling to elicit antithrombotic effects at the clotting site. In vivo studies show these unique properties converge to allow subcutaneous nanogranule depots to extend heparin serum concentrations for an order of magnitude longer than standard dosing regimens while enabling prolonged and controlled anticoagulant activity. This biohybrid delivery system demonstrates a potentially scalable platform for the development of safer, easier to administer, and more effective antithrombotic nanotechnologies.

更新日期：2022-10-03

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