Leech bionic Hirudin fusion protein prodrug loaded microneedles for long-term inhibition of thrombosis
Basic science / preclinical published in Journal of controlled release : official journal of the Controlled Release Society (2025)
Abstract
The clinical use of anticoagulant drugs for thrombosis is limited by short half-life and bleeding risk, requiring frequent administration and close monitoring. Here, inspired by leech mouthparts, we present a hirudin-based fusion protein prodrug incorporated with microneedles (MNs) for long-term antithrombotic therapy to achieve a simplified dosing regimen, continuous protection, and on-demand antithrombotic bioactivity recovery. Genetic-engineered anticoagulant prodrugs are precisely customized by fusing hirudin to elastin-like polypeptides with adjustable assembly characteristics. The introduction of elastin-like polypeptides can shield the biological activity of hirudin, drive the self-assembly of fusion proteins, and prolong their half-life in vivo. The fusion protein prodrugs circulate in the blood as sentinels and accumulate in the thrombus site with the assistance of the clot-targeted motif. Under the catalysis of FXa during thrombosis, the fusion protein prodrugs adaptively restore anticoagulant activity to inhibit thrombus formation. Notably, the assembled prodrugs were integrated into an MN matrix made of silk fibroin and chitosan through photopolymerization for long-term controlled release and facile self-administration. It was proved that the bionic MNs conveniently provide long protection against thrombosis without increasing bleeding events. These excellent performances indicate that the bionic MN patch has broad application prospects in thrombosis and related diseases.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
The clinical use of anticoagulant drugs for thrombosis is limited by short half-life and bleeding risk, requiring frequent administration and close monitoring.
Por qué esto importa para la hirudoterapia
Este estudio diseñó un profármaco de proteína de fusión basado en hirudina incorporado en parches de microagujas para terapia antitrombótica a largo plazo, con inspiración de diseño tomada de las piezas bucales de la sanguijuela. El enfoque fusiona la hirudina con polipéptidos tipo elastina que protegen su actividad anticoagulante durante la circulación, prolongan la semivida in vivo y permiten el autoensamblaje, mientras que un motivo dirigido al coágulo y una activación sensible al Factor Xa restauran la función anticoagulante específicamente en los sitios del trombo. Este trabajo es relevante para el ámbito de ASH porque aprovecha la hirudina dentro de una plataforma de administración bioingenieril orientada a superar las limitaciones de los anticoagulantes convencionales, incluida la semivida corta y el riesgo de hemorragia. Sin embargo, el estudio no involucra sanguijuelas vivas y utiliza hirudina recombinante obtenida por ingeniería genética en lugar de secreciones salivales totales; aunque se reportan hallazgos in vivo, el resumen proporciona datos cuantitativos limitados sobre los resultados, y no se describen resultados clínicos en humanos.
Citación
Leech bionic Hirudin fusion protein prodrug loaded microneedles for long-term inhibition of thrombosis.
Tian X et al. · Journal of controlled release : official journal of the Controlled Release Society, 2025
Contexto clínico relacionado
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Añadido a la biblioteca ASH: March 18, 2026 · Última actualización del sitio: June 18, 2026