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
This study developed a nonviral gene delivery system using PEGylated PAMAM dendrimers modified with RGDyC to carry recombinant hirudin (rHV) plasmid DNA for thrombus-targeted therapy. The system achieved 7.56-fold higher transfection efficiency than lipofectamine 2000 in HUVEC cells and reduced thrombus weight in a Wistar rat venous thrombosis model, with antithrombotic efficacy comparable to heparin (P > 0.05). For ASH's domain, this demonstrates a novel engineering approach to localize hirudin expression at thrombus sites, potentially increasing therapeutic concentration while reducing bleeding risk. However, this is a preclinical study in rats and cell culture using a gene therapy strategy rather than live leech therapy or the leech secretome directly; no clinical or human efficacy data are presented.
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: June 18, 2026