Targeting Nanotechnologies for the Treatment of Thrombosis and Cardiovascular Disease

Abstract

Thrombosis is characterized by the formation of in vivo blood clots that are localized within arterial or venous blood vessels. These thrombi form beyond the need for physiologically healthy hemostatic responses and can lead to significant medical issues for affected individuals. Unfortunately, the existing standard-of-care therapies for treating thrombosis are systemic in their therapeutic design; therefore, they interfere with the patient's physiological hemostasis. Examples of the severe clinical side effects commonly associated with currently available therapies include, but are not limited to, bleeding complications. Therefore, there is a profound demand for novel therapeutic interventions that can circumvent these debilitating complications, while offering improved therapeutic efficacy. Recent advancements in nanotechnology present an opportunity to develop novel and improved drug delivery systems to meet this clinical demand. Preclinical investigations have begun to uncover the potential of nanotechnology, particularly in the treatment of thrombosis and also in nonhemostatic cardiovascular diseases. This article reviews recent preclinical studies aimed at developing a diverse array of different nanotechnologies for treating thrombosis as well as heart diseases. This review will also outline the limitations with current nanotechnologies and what challenges need to be overcome to translate these novel therapies to the clinic.

Bioresponsive Polyphenol-Based Nanoparticles as Thrombolytic Drug Carriers

“…Nanoparticle technologies continue to demonstrate immense promise in delivering thrombolytic therapy to treat thrombotic disease, which includes offering improved efficacy and reduction in serious complications. 23 Furthermore, the encapsulation of thrombolytic agents in NPs offers the potential to design prophylactic therapeutic approaches for administering thrombolytic therapy, which is not currently available due to the inherent risks involved with free thrombolytic agents in circulation. The successful implementation of a prophylactic therapeutic approach for thrombolytic therapy offers future thrombosis patients with an increased chance of survival and improved quality of life post-diagnosis.…”

“…Thrombolytic drugs are designed to enrich and selectively act at sites of pathological thrombosis, sparing healthy hemostatic processes. Accordingly, much effort has been devoted to realizing the site-specific delivery of PAs by exploiting the biological microenvironment of thrombi, including high shear stress levels, , associated coagulation factors, such as thrombin, , and active targeting against thrombi-specific markers. , Emerging nanotechnologies demonstrate their potential for achieving enhanced thrombolytic treatment outcomes offering improved safety profiles; these include the development of magnetic nanoparticles (NPs), electrostatically charged NPs, as well as lipid-based NPs . These NPs are aimed at improving PA loading capacities and serving as a thrombin-responsive drug delivery platform to transport PAs locally to thrombi.…”

Recent Advances in Cell‐Based Nanotherapy for Cardiovascular Diseases

“…Thrombosis is one of the most common potential pathologies in CVDs and is usually formed by excessive blood clot in the arterial and venous systems. [51] Clinical therapies involve systemical administration of thrombolytic drugs (i.e., tissue plasminogen activator (tPA) and heparin) to dissolve thrombus and keep blood flowing. [52][53][54] Unfortunately, current anti-thrombotic therapies are easy to trigger fatal side effects, which enormously reduce life quality of patients.…”

“…Multifarious nanoformulations are developed to ensure that therapeutic agents are concentrated at thrombi site and to decrease side effects. [51,55] Some specific peptides or small molecules (e.g., fucoidan, fibrin-specific peptides) have been applied for NPs' surface modification to enhance their selectivity for thrombus site or targeting cells. [8,14,23,56] Compared with the small specific molecules modified DDSs, cell-based nanotherapy is a more efficient strategy to enhance specificity and biocompatibility for antithrombotic or thrombolytic therapy.…”

Mopping up crystals to keep the blood flowing

“…Nanomedicine, a rapidly developing field with some remarkable preclinical achievements so far, holds a lot of promise in the delivery of more potent and specific therapies for atherosclerosis. 3 The range of activities in the field has significantly increased over the last decade thanks to substantive investments and the emergence of new companies focusing exclusively on nanotechnology. In recent years, there has been a clear trend to use particle systems inspired by nature.…”