Abstract Number: OC 08.4
Meeting: ISTH 2020 Congress
Theme: Diagnostics and OMICs » Nanotechnology and Novel Biomolecules
Background: Intravenous injection of thrombolytic agents, such as tissue plasminogen activator (tPa), can be used to enzymatically breakdown the blood clot to re-establish blood flow through the affected vessel. However the use of thrombolysis is currently limited by its short time window of efficacy, and the risk of life-threatening haemorrhage. Iron oxide nanoparticles (IONPs) can be heated by exposure to an external alternating magnetic field. These IONPs can be conjugated with peptides and antibodies to allow their targeting to blood clots.
Aims: To investigate whether magnetic hyperthermia (MH) induced by platelet-targeted IONPs (P-IONPs) could be used to enhance the efficacy of tPa-mediated thrombolysis.
Methods: PAC-1 antibody was conjugated to citrate-coated IONP to generate platelet-targeted magnetic nanoparticles. Ex vivo generated human blood clots and 3D HUVEC cell cultures were incubated with the P-IONPs and then exposed to tPa in the presence or absence of magnetic stimulation. Clot structure and permeability were assessed by confocal and electron microscopy. ANOVA and Student’s t-test were used to assess statistical significance.
Results: MH induced by P-IONPs was found to increase the permeability of blood clots to 70 kDa fluorescent dextran (138 ± 17% of control, n = 10, P < 0.05). MH enhanced the thrombolytic activity of tPa - reducing the weight of tPa + MH treated clots to 75.6 ± 1.5 % of untreated control clots, compared to 81.3 ± 2.2% of control in clots treated with tPa alone (n = 15, P < 0.05). Using electron microscopy, MH was observed to enhance tPa-mediated clot disruption. There was no observable increase in cell death of HUVEC cell cultures exposed to P-IONP-mediated MH.
Conclusions: Platelet-targeted magnetic nanoparticles could act as an adjuvant to enhance the efficacy of current thrombolytic therapies through the induction of localised MH.
Supported by the Wellcome Trust (207617/Z/17/Z).
To cite this abstract in AMA style:
Cabrera D, Sharifabad M, Telling N, Harper A. Platelet-targeted Magnetic Nanoparticles Enhance the Efficacy of Thrombolysis through Induction of Magnetic Hyperthermia [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/platelet-targeted-magnetic-nanoparticles-enhance-the-efficacy-of-thrombolysis-through-induction-of-magnetic-hyperthermia/. Accessed March 21, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-targeted-magnetic-nanoparticles-enhance-the-efficacy-of-thrombolysis-through-induction-of-magnetic-hyperthermia/