Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy
Drug delivery study published in Molecular Pharmaceutics (2019)
Abstract
This study proposed a new nonviral gene delivery system for thrombus targeting therapy based on PEGlyation polyamides dendrimer (PAMAM) modified with RGDyC to condense the pDNA with recombinant hirudine (rHV) gene (RGDyC-rHV-EGFP). The RGDyC-mPEG-PAMAM was synthesized and characterized by 1H NMR, PAMAM/pDNA was characterized by particle size, zeta potential, cellular uptake, and gel retraction assay. The transfection was carried out between lipofectamine 2000 and PAMAM/pDNA on HUVEC cells at various N/P ratios. The antithrombotic effect in vivo was evaluated by venous thrombosis model on Wistar rats. It showed that the drug delivery system of RGDyC modified PAMMA, which entrapped pDNA could significantly improve the transfection efficiency. It was about 7.56-times higher than that of lipofectamine 2000. In addition, the expression level of hirudine fusion protein was the highest at N/P ratio of 0.5. The results of antithrombotic effect showed that the weight of thrombus was reduced in RGDyC modified group; compared with heparin group, there was no significant difference ( P > 0.05). Overall, we take the advantage of the unique advantages of hirudine, combining the genetic engineering, nanocarriers, and targeting technology, to achieve the targeted enrichment and activation the hirudine fusion protein in the thrombus site, to improve the concentration of drugs in the thrombus site, finally increasing the curative effect and reduce the risk of bleeding. The strategy of gene delivery system holds unique properties as a gene delivery system and has great promises in thrombus targeting therapy.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
RGDyC-modified PEGylated PAMAM dendrimer delivered recombinant hirudin gene to thrombus sites with 7.56-fold higher transfection efficiency than lipofectamine; in-vivo venous thrombosis weight was reduced equivalent to heparin.
Por qué esto importa para la hirudoterapia
Este estudio desarrolló un sistema de liberación génica no viral mediante dendrímeros PAMAM PEGilados modificados con RGDyC para vehiculizar ADN plasmídico de hirudina recombinante (rHV) destinado a la terapia dirigida al trombo. El sistema alcanzó una eficiencia de transfección 7,56 veces mayor que la del lipofectamina 2000 en células HUVEC y redujo el peso del trombo en un modelo de trombosis venosa en ratas Wistar, con una eficacia antitrombótica comparable a la de la heparina (P > 0,05). Para el dominio de ASH, esto demuestra un enfoque de ingeniería novedoso para localizar la expresión de hirudina en los sitios de trombosis, aumentando potencialmente la concentración terapéutica y reduciendo el riesgo de sangrado. No obstante, se trata de un estudio preclínico en ratas y cultivo celular que emplea una estrategia de terapia génica en lugar de la terapia con sanguijuelas vivas o del secretoma de la sanguijuela de forma directa; no se presentan datos de eficacia clínica ni en humanos.
Citación
Novel Strategy of Gene Delivery System Based on Dendrimer Loaded Recombinant Hirudine Plasmid for Thrombus Targeting Therapy.
Chen J et al. · Molecular Pharmaceutics, 2019
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Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026