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Review
. 2015 Nov 1;1(4):FSO46.
doi: 10.4155/fso.15.46. eCollection 2015 Nov.

Nanomedicine as a strategy to fight thrombotic diseases

Mariana Varna  1 , Maya Juenet  1 , Richard Bayles  2 , Mikael Mazighi  3 , Cédric Chauvierre  1 , Didier Letourneur  1
Affiliations
Review

Nanomedicine as a strategy to fight thrombotic diseases

Mariana Varna et al. Future Sci OA. .

Abstract

This review highlights the preclinical and clinical research based on the use of nano- and micro-carriers in thrombolytic drug delivery. Ischemic heart and stroke caused by thrombosis are the main causes of death in the world. Because of their inactivation in the blood, high doses of thrombolytics are administered to patients, increasing the risk of intracranial hemorrhage. Preclinical research conducted with lipid, polymer or magnetic nanoparticles loaded with thrombolytic drugs showed an enhancement of thrombolysis and a reduction of undesirable side effects. Targeted nanocarriers exhibited an increased accumulation into clot. Clinical trials were already conducted with lipid-based microbubbles combined with ultrasound and thrombolytic drug and showed thrombolysis improvement. Future validation of nanosystems is awaited in clinic. This research opens new strategies for the management of thrombotic diseases.

Keywords: animal models; drug delivery; ischemic heart; microbubbles; nanocarriers; stroke; thrombolytic.

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Conflict of interest statement

Financial & competing interests disclosure This work was supported by Lefoulon-Delalande scholarships (to M Varna and R Bayles), EU project NanoAthero FP7-NMP-2012-LARGE-6–309820, IMOVA project (FUI/OSEO, CG93), and ANR-13-LAB1–0005–01 ‘FucoChem’, University Paris 13 and Inserm. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Atherosclerotic plaque development.
(A) Cholesterol derived low-density lipoproteins extravasate in the intima where they are oxidized low-density lipoproteins. Endothelial cells are activated and express specific adhesion molecules. These phenomena drive the recruitment of monocytes which differentiate into macrophages expressing scavenger receptors, and the uptake oxidized low-density lipoproteins. Smooth muscle cells migrate into the intima, proliferate and contribute to foam cell formation. (B) In advanced stages, a fibrous cap made of smooth muscle cells and collagen fibers is formed. Apoptotic events and necrotic zones appear in a hypoxic environment inducing new microvessel development. With plaque rupture thrombogenic substances are released into the circulation and promote platelet activation and adhesion to endothelium and thrombus formation.
<b>Figure 2.</b>
Figure 2.. Schematic representation of fibrin clot thrombolysis induced by thrombolytic agents in blood vessels.
<b>Figure 3.</b>
Figure 3.. Schematic representation of polymer-, magnetic- and lipid-based stealth nanocarriers loaded with thrombolytic drugs.
<b>Figure 4.</b>
Figure 4.. Targeting modality by peptides.
Nanocarriers loaded with thrombolytic drugs and decorated with RGD peptides that recognize GPIIb/IIIa receptor at the surface of activated platelets, show an accumulation in the thrombus and leading to an enhancement of thrombus lysis.
<b>Figure 5.</b>
Figure 5.. Targeting modality by magnet.
Ultrasmall paramagnetic iron oxide nanocarriers loaded with thrombolytic drugs are concentrated by an external magnet in the thrombus to enhance its lysis.
<b>Figure 6.</b>
Figure 6.. Schematic representation of thrombus dissolution by ultrasound.
See this image and copyright information in PMC

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