Nanomedicine targeting Atherosclerosis

As nanotechnologies enter the arena of clinical medicine, new routes for applying nanomedicine to cardiovascular health issues are emerging. Although much research has been undertaken in the cardiovascular field for the pathogenesis of atherosclerosis, there is still a lack of imaging modalities for early diagnosis and acute intervention of the disease. The complexity of its pathogenesis makes it difficult to develop effective therapeutic strategies that are applicable in clinical routine.

Clinical hurdles

Numerous clinical trials have indicated that vulnerable plaques (ie. those highly inflamed and with tendency for rupture) often do not cause noticeable luminal obstruction or symptoms before an acute event occurs. This causes plaque rupture to be unpredictable with common diagnostic tools that focus on luminal narrowing. Hence, the current diagnostic paradigms for the non-invasive detection of such plaques are inadequate.

In clinical practice, the angioplasty with stent implantation is the invasive procedure to treat the arterial stenosis. Drug eluting stents (DES) have been used as vehicles for site-specific drug delivery in order to circumvent restenosis. However, late thrombosis, inflammation and endothelium healing delay are of major concern. It has been shown that the polymer coatings and anti-proliferative drugs employed by DES impair stent strut endothelialisation and may induce stent thrombosis.

Nanomedicine advances and challenges

Nanomedicine employs converging technologies to improve human health, and nanoparticles (NPs) exhibit diagnostic and therapeutic moieties for site-specific targeting. Especially in the size range of 10-100 nm, NPs exhibit a large surface area to volume ratio that enables the conjugation of multiple diagnostic and therapeutic agents and their interactions with cell membrane receptors, peptides, etc. When conjugated with targeting ligands, they can be used to target specific cells with high specificity and affinity. Their small size allows them to navigate through the blood vessels and deliver their cargo within the plaques.

New contrast agents allying nanotechnologies with existing technologies are currently under development. Diverse NPs (including fluorescent, radioactive, paramagnetic, superparamagnetic, liposomes, etc.) have been utilised for plaque imaging. The most frequently used targets are related to plaque composition and the process of inflammation, thrombosis and angiogenesis.

The nanotechnology strategies for stents optimisation involve the development of nanomaterials with unique surface properties that resemble the nanostructure of endothelium and of nanocarriers to deliver drugs at the diseased sites. Our group developed a nanoporous platform that can elicit multiplex drugs in a controllable and sustainable manner.

Future perspectives

NPs that hold both diagnostic and therapeutic agents are popularly referred to as theranostic NPs. A nanotheranostic strategy may have significant benefits in the simultaneous diagnosis and treatment of the plaques by monitoring the NPs biodistribution in the body over time, their penetration through endothelium, and their interactions with the target cells. One major challenge is to achieve an efficient arterial localisation of the NPs – an optimum dosing required for imaging and therapy in line with limited nanotoxicity to guarantee their clinical applicability. As the nanomedicine market matures and innovations move from bench to bedside, novel strategies will be discovered to master atherosclerosis.

Atherosclerosis: a nano-disease

Atherosclerosis is a systemic and chronic inflammatory disease that may cause arterial stenosis and the clinical manifestations of angina, heart attack and stroke. It results from an initial endothelium dysfunction with further enhancement of oxidative stress, lipids and monocyte recruitment.
The pathophysiology of the disease implies its ‘nanoscale’ nature and therefore necessitates new nanomedicine approaches to combat it.

Article from Dr Varvara Karagkiozaki and Professor Stergios Logothetidis from the Nanomedicine Group, Nanotechnology Lab-LTFN, Aristotle University of Thessaloniki, Greece, first released in the publication “International Innovation” –