Review
Emerging applications of
nanomedicine for the diagnosis and
treatment of cardiovascular diseases
Biana Godin1, Jason H. Sakamoto1, Rita E. Serda1, Alessandro Grattoni1,
Ali Bouamrani1 and Mauro Ferrari1,2,3
1
The University of Texas Health Science Center at Houston (UTHSC-H), Department of NanoMedicine and Biomedical Engineering,
1825 Pressler, Suite 537, Houston, TX 77030, USA
2
The University of Texas MD Anderson Cancer Center, Department of Experimental Therapeutics, Unit 422, 1515 Holcombe Blvd.,
Houston, TX 77030
3
Rice University, Department of Bioengineering, Houston, TX 77005, USA
Nanomedicine is an emerging field that utilizes nano-
technology concepts for advanced therapy and diagnos-
tics. This convergent discipline merges research areas
such as chemistry, biology, physics, mathematics and
engineering. It therefore bridges the gap between mol-
ecular and cellular interactions, and has the potential to
revolutionize medicine. This review presents recent
developments in nanomedicine research poised to have
an important impact on the treatment of cardiovascular
disease. This will occur through improvement of the
diagnosis and therapy of cardiovascular disorders as
atherosclerosis, restenosis and myocardial infarction.
Specifically, we discuss the use of nanoparticles for
molecular imaging and advanced therapeutics, specially
designed drug eluting stents and in vivo/ex vivo early
detection techniques.
Introduction
Despite significant clinical advancements, cardiovascular
diseases (CVDs), which include various disorders of blood
vasculature and the heart, as well as stroke, remain the
leading cause of death in the USA. Based on statistics
provided by the National Institutes of Health (NIH) and
the American Heart Association, 80 million people in the
USA suffer from CVDs and >35% of deaths in North
America are attributed to CVDs (http://www.nhlbi.nih.gov;
www.americanheart.org). The last breakthrough technol-
ogy to impact CVDs occurred over a decade ago with the
introduction of the coronary stent by Palmaz and Schatz,
which was approved by the Food and Drug Administration
(FDA) in 1994. Since then, medicine has relied upon new
‘blockbuster’ therapeutics (e.g. statins, beta-blockers,
diuretics) and refinements of surgical procedures such as
percutaneous transluminal coronary angioplasty (PTCA),
coronary artery bypass grafts (CABG) and stenting to treat
CVDs. However, current methods for early detection and
advanced therapies of CVDs are limited, and their effi-
ciency in preventing CVDs questionable.
By definition, nanotechnology involves two inter-related
constituents: (i) nanoscale dimensions of the whole system
Corresponding author: Ferrari, M. (Mauro.Ferrari@uth.tmc.edu).
0165-6147/$ – see front matter . Published by Elsevier Ltd. doi:10.1016/j.tips.2010.01.003 Available online 19 February 2010
or its vital components; (ii) man-made nature and unique
characteristics of new material that arise due to its nano-
scopic size [1,2]. Nanotechnology represents a convergent
discipline in which the margins separating various
research areas, such as chemistry, biology, physics, math-
ematics and engineering, become blurred. Cardiovascular
nanomedicine is likely to face and address current chal-
lenges in CVDs. It will also improve detection and therapy
by advancing the ex-vivo and in-vivo detection and imaging
of biomarkers, as well as by directed/improved delivery of
drugs and tissue regeneration [3].
We will summarize and discuss recent developments in
nanotechnology for the detection and therapy of CVDs
focusing on nanoparticles, specially designed therapeutic
and tissue regeneration devices, and in-vivo/ex-vivo early
detection techniques (Figure 1).
Nanoparticles for advanced diagnostics and treatment
of CVDs
Various nanoparticle-based drug-delivery systems have
been and are being developed for applications in cancer,
CVDs and other conditions. These have different features
and multiple-functionalities [2,4–6], exhibiting differences
in: (i) sizes, ranging from few tens of nanometers (e.g.
dendrimers, gold and iron-oxide nanoparticles) to few hun-
dreds of nanometers (e.g. polymeric and lipid-based
particles) to micron-sized particles; (ii) shapes, from the
classical spherical particles to discoidal, hemispherical,
cylindrical and conical; (iii) surface functionalizations, with
a broad range of electrostatic charges and bio-molecule
conjugations. Use of nanocarriers for these conditions allows
for local or directed delivery, prolonged effect of the drug,
facilitated delivery into target cells, and reduction of the
shear effects of blood flow. During the course of develop-
ment, atherosclerotic plaques and the neointima display
various stage-specific molecules that can be used as target-
ing moieties in CVDs (avb3-integrin, VCAM-1, YIGSR).
Nanoparticles for advanced diagnostics of CVDs
One of the major foci of the application of nanotechnology
for cardiovascular research has been the directed imaging
and therapy of atherosclerosis, restenosis and over cardi-
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Figure 1. Nanotechnology approaches for the advanced diagnosis and treatment of CVDs (schematic): Nanoparticles for (A) multimodal image contrast and (B) improved
treatment of CVDs can be targeted to immune cells or specific ligands on the inflamed endothelium of the atherosclerotic plaque; (C) in-vivo sensors implanted in the
pericardial region or on one of the main blood vessels and techniques for ex-vivo detection of biomarkers; (D) nanostructured drug/nanoparticle-eluting stents.

ovascular conditions. Nanoscale contrast agents have
emerged as multifaceted modalities that can be used to
identify and characterize the early stages of disease before
the development of pathological manifestations. Contrast-
generating nanomaterials for cardiovascular imaging in-
clude fluorescent, radioactive, paramagnetic, superpara-
magnetic, electron-dense and light-scattering particles
(Table 1).
Cardiovascular imaging by magnetic resonance imaging
(MRI) requires powerful magnetic fields and radiofre-
quency waves to generate images of internal structures.
Energy changes in tissue in response to the magnetic field
are detected and the presence of contrast agents amplifies
these changes. Three MRI techniques are T1, T2*, and off-
resonance [7]. Off-resonance imaging relies on pulse
sequences that excite and refocus off-resonance water,
leading to positive contrast [8]. Paramagnetic contrast
agents such as gadolinium chelates (e.g. gadolinium-
diethylenetriaminopentaacetic acid (DTPA)) enhance T1
contrast, resulting in bright contrast in MR images [9].
Manganese nanoparticles represent another, recently
introduced, example of T1-enhancing contrast agent
[10,11]. Superparamagnetic contrast agents such as iron
oxide (IO) nanoparticles, predominately magnetite (Fe2O3/
Fe3O4), typically enhance T2 contrast and produce dark
contrast [8]. The technique of choice is dependent upon the
application and the weight of sensitivity, specificity and
artifact minimization such as bright contrast originating
from perivascular fat on atherosclerotic plaque images [9].
Nanoparticles have size-dependent imaging properties.
For example, intrinsically fluorescent nanoparticles
(‘quantum dots’) emit light over a broad range from
near-ultraviolet to mid-infrared. Increases in particle size
are positively correlated to increases in emission wave-
length [12]. Microparticle-based contrast agents for ima-
ging include porous silicon particles that encapsulate
abundant IO nanoparticles in a single unit for enhanced
contrast [13]. These multistage particles (as well as other
particles that are candidates for phagocytosis by macro-
phages) offer imaging of inflamed areas where macro-
phages accumulate (e.g. atherosclerotic plaques) [14].
The feasibility of multi-modal imaging with nanoparticles
containing multiple contrast agents such as 18F-cross-
linked iron oxide (18F-CLIO) nanoparticles [15,16] has
been demonstrated. 18F-CLIO agents consist of a cross-
linked dextran shell formed on a superparamagnetic IO
core and functionalized with the radionuclide 18F. These
particles can be detected with positron emission tomogra-
phy (PET), fluorescence molecular tomography, and MRI.
Chen et al. [17] examined in-vivo MRI contrast of vulner-
able plaque high-density lipoprotein (rHDL) nanoparticles
enriched with Gd-based amphiphiles and a targeting

Table 1. Examples of contrast-enhancing nanoparticles for imaging of CVDs

Category Agent (examples) Imaging techniques References
Fluorescent Quantum dots Fluorescence tomography [12]
18
Radioactive F CLIO, 111In nanoparticles PET, SPECT [15]
Paramagnetic Gd-DTPA MRI [17]
Superparamagnetic Iron oxide nanoparticles MRI [21]
Electron-dense Gold or I-based nanoparticles CT [18,19,78,79]
Light-scattering Gold nanoshells Optical coherent tomography [80]
Photoacoustic Colloidal nanobeacons Photoacoustic tomography [81]
Multimodal Copper-CLIO PET, MRI, NIRF [16]
Perfluorocarbon nanoparticles MRI, Molecular imaging [33,82]
CLIO: cross-linked iron oxide; PET: positron emission tomography; SPECT: single-photon emission computed tomography; Gd-DTPA: gadolinium chelated with diethylene-
triamine pentetic acid; MRI: magnetic resonance imaging; CT: computed tomography; NIRF: near-infrared fluorescence.

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moiety to intra-plaque macrophages (apolipoprotein E-
derived lipopeptide, P2fA2). Data showed a significant
enhancement in MRI signal of the atherosclerotic wall
24 h after the 50 mmol Gd/kg injection of rHDL-P2fA2
relative to administration of rHDL (90% vs 53% enhance-
ment, respectively).
An interesting set of studies explored the use of nano-
liposomes as carriers for contrast agents such as iodine for
MRI and computed tomography (CT) [18,19]. These sys-
tems were shown to efficiently prevent a rapid clearance of
the contrast agent from the body, significantly improving
capabilities of the total blood pool and cardiac imaging in
animal models. For example, with improved liposomal
formulation of iodine, time–attenuation curves showed
an initial enhancement of about 900 H in the aorta
and plateau levels of 800 H were achieved after 2 h,
indicating a high iodine concentration in the blood pool.
These blood levels of liposomal iodine enabled excellent
contrast discrimination between the myocardium and
blood in the right and left ventricles, aorta, pulmonary
trunk, and inferior vena cava with substantially lower
liver and spleen contrast, as would be expected from the
delayed clearance of polyethylene glycol (PEGylated) lipo-
somal iodine formulation via the reticulo-endothelial sys-
tem. The long residence time at stable, high opacity makes
liposomal iodine a promising effective micro-CT agent for
contrast enhancement within sub-millimeter vessels, and
no significant renal clearance [18,19] making CT another
emerging field where nanoparticles have been shown to
increase imaging contrast [20].
FDA-approved nanoparticles for imaging are limited to
three IO formulations (AMI-121 (FerumoxsilTM), OMP50,
and AMI-25 (FeridexTM)) targeted to the gastrointestinal
tract, liver and spleen. Injection of high doses of iron was
shown to be non-toxic in the nanoparticle formulation due
to slow release of free iron and assimilation into iron-
containing substances [21].
Targets for imaging of atherosclerotic plaques include
endothelia, macrophages [22], fibrin [23], collagen III [24],
and markers of angiogenesis (Figure 1A). Fibrin deposition
is one of the earliest signs of plaque rupture, and fibrin, as
well as tissue factor, are targets for imaging arterial
thrombi by ultrasound [25] and MRI [26]. One example
of angiogenesis targeting is the use of nanoparticles con-
jugated to ligands that specifically interact with avb3-
integrin [27].
Therapeutic and theranostic nanoparticles
Various nanotechnology applications are being investi-
gated for the treatment of atherosclerosis and restenosis,
including nanocarriers for drug delivery (Figure 1B) and
devices such as mechanical stents, possessing nanoscale
components (Figure 1D; see below). Among the drugs used
to prevent restenosis are cytotoxics that inhibit the growth
of smooth muscle cell (e.g. paclitaxel, cytarbine, etoposides,
doxorubicin), platelet-derived growth factor (PDGF) recep-
tor antagonists (e.g. tyrphostins), inhibitors of the inflam-
matory response/immunomodulators (e.g. steroids,
bisphosphonates, cyclosporine A), and antibiotics (e.g.
fumagillin). Other promising therapeutics affect specific
gene targets responsible for thrombosis or intimal hyper-
plasia (e.g. prostacyclin synthase and thymidine kinase).
In the case of genetic materials and other biomolecules,
their encapsulation in nanoparticles provides protection
from enzymatic degradation and allows for prolonged
release profiles. These therapeutic strategies have been
thoroughly reviewed. [28,29].
The main nanocarrier classes investigated as thera-
peutic and ‘theranostic’ (i.e. particles integrating diagnos-
tic imaging and therapeutic components) agents for
restenosis are liposomes with different surface character-
istics, polymeric nanoparticles and micelles, perfluorocar-
bon nano-emulsions and cross-linked iron oxide (CLIO)
particles conjugated to therapeutic molecules [30–34].
Examples of these classes are given in Table 2.
Theranostic agents have gained much recent interest as
a valuable advance for drug delivery [35]. This strategy for
CVD applications is still in its infancy, but it has numerous
potential advantages which are being extensively investi-
gated in cancer nanomedicine. Combining a diagnostic
imaging moiety with a targeted therapeutic nanoparticle
allows for precise, temporal and spatial monitoring of the

Table 2. Examples of nanocarriers for CVD therapy

Nanocarrier
Neutral liposomes
Cationic liposomes
Hemaglutin virus of Japan
(HVJ) liposomes
Perfluorocarbon nanoparticles
Polyelectrolyte nanoparticles
(RNA or polyvinyl sulfate with
polyethylene imine/DNA complex)
Polymeric (PLA or PLGA) nanoparticles
Example of agent Experimental model Outcomes References
Bisphosphonates Injured carotid artery in rats Macrophage depletion, [30]
(clodronate, alendronate) reduced inflammation
Chloramphenicol acetyl Balloon-injured artery in Increased expression [31,32]
transferase (CAT) encoding Yorkshire pigs, local delivery of CAT
gene [31]
Vascular endothelial Clinical trial, patients with Significant improvement
growth factor (VEGF) 60–99% stenosis in major in myocardial perfusion
encoding viral vector arteries, local delivery
through catheter
Tissue factor pathway Iliac artery of hyperlipidemic Reduction of intimal [83]
inhibitor gene rabbits after angioplasty. hyperplasia
Local delivery through catheter.
Surface bound Human plasma clots, In-vitro fibrinolysis, [82]
streptokinase, a3b hyperlipidemic animals theranostic in vivo
integrins, others
Gene encoding for Rat carotid artery High transfection efficiency [84]
urokinase plasminogen
activator
AG-1295 and AGL-2043 Balloon-injured Inhibition of restenosis [85,86]
carotid artery in rats

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therapeutic agent as well as treatment outcomes. The
imaging capabilities of theranostic nanoparticles can serve
to verify delivery of an active compound to its intended site
of action; monitor and quantify the efficacy of the thera-
peutics at the molecular or cellular level; design dosing
regiments; and identify the population of responders/non-
responders for a specific therapy. For example, a prolonged
anti-angiogenesis therapy was reported using theranostic
avb3-integrin-targeted paramagnetic nanoparticles in
hyperlipidemic animals [33,36,37]. MRI data showing a
reduction of 50–75% in the neovascular signal for 3 weeks
corresponded well with histological evaluation, pointing
toward the potential of this strategy for efficient anti-
angiogenic therapy and simultaneously evaluating plaque
stability. Another example is a system based on fibrin-
coated perfluorocarbon nanoparticles which can be used for
acoustic or MRI imaging with targeted thrombolysis [38].
There is also the opposite side of interaction of nano-
particles with the walls of blood vessel. The vascular
endothelium could be a barrier and unwanted target for
nanoparticles to be delivered to other organs [39]. In this
respect, CVDs may affect the transport of nanoparticles
across vessel walls, organelle-targeted delivery of nano-
particles, and other effects of nanoparticles on vessel cells.
These factors should be taken into account in future nano-
medical research.
Devices for ex-vivo and in-vivo early detection of CVD
indicators
Along with the development and adoption of novel strat-
egies for treatment and prevention of CVDs, efforts are
being spent to apply nanotechnologies for ex-vivo and in-
vivo detection of CVD signals (Figure 1C). The ability to
monitor for precursor signals of CVDs could potentially
reduce the many fatalities associated with the diseases.
For example, monitoring thrombotic or hemorrhagic
events could facilitate the diagnosis and treatment of
stroke and embolisms. Measurement of variations in the
pressure and flow of blood, biomolecule concentration or
ion concentration could provide insights in the understand-
ing of cardiovascular events.
Nanotechnology for the ex-vivo harvesting and
detection of biomarkers
Identification of biomarkers provides a powerful approach
for screening, diagnosis, prognosis and therapeutic
monitoring [40]. Addressing the underlying causes of
CVDs and improving the detection of early-stage disease
permitd early intervention with more efficient disease
management and a significant reduction in premature
mortality. Development of high-performance ‘point of care’
methods will improve the prognosis for CVD patients by
obtaining more sensitive, more specific, and faster assess-
ment of diagnostic markers. Several authors have reported
an interest in using individual biomarkers of CVDs to
better identify high-risk populations. These markers in-
clude C-reactive protein [41], B-type natriuretic peptide
[42], fibrinogen [43], D-dimer [44], and homocysteine [45].
Wang et al. reported simultaneous measurement of several
biomarkers to enhance risk stratification [46]. They con-
cluded that the use of current biomarkers (even in a multi-
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Trends in Pharmacological Sciences Vol.31 No.5
detection approach) only moderately improves standard
assessment. There is, therefore, an urgent need for tech-
nological advances in biomarker strategies to improve the
detection of markers and to discover new biomarkers.
In medical applications, the use of nanotechnology pre-
senting unique physical and chemical properties has the
potential to dramatically advance diagnostic methods and
provide innovative devices for more efficient molecular
detection. Tunable nanoporous materials have been used
to selectively harvest low-molecular-weight proteins, pro-
viding a unique opportunity to detect and identify new
circulating biomarkers after fractionation of body fluids
[47,48]. Nanowires offer great potential for diagnosis by
measuring pH variations or detecting trace amounts of
biological and chemical species [49]. Nanocantilevers can
be used as multiple label-free assays for the detection of
DNA species or circulating protein biomarkers [50].
A high-specificity immunoassay-based diagnostics
device combining impedimetric analysis nanoelectrodes
and microfluidics has been developed to measure the con-
centration of D-dimer (a recognized biomarker of increased
blood clotting activity in deep-vein thrombosis (DVT)) in
whole blood [51]. This device could improve the accuracy
and reliability of early assessment of patients at risk of
DVT. Other ‘lab-on-a-chip’ approaches have been devel-
oped in combination with nanotechnology to improve the
sensitivity and accuracy of biomarker detection. Associ-
ated with analysis by electrocardiography (ECG), a saliva-
based biomarker test within a lab-on-a-chip platform
exceeded the screening capacity of ECG alone, providing
rapid screening for acute myocardial infarction (AMI) [52].
Another study demonstrated the use of a rapid fluoro-
phore-mediated immuno-sensing system for simultaneous
quantification of four cardiac markers in AMI patients.
This technology is based on a micro-electro-mechanical
system (MEMS) and nanoparticle reagents that increase
detection sensitivity [53].
Isoforms of troponins are structural proteins that are
unique to cardiac myocytes (cardiac troponin I and T).
These proteins are tissue-specific, and the immuno-detec-
tion of their cardiac forms has become a standard in the
diagnosis of myocardial infarction [54]. A clinical report
using a novel ultra-sensitive nanoparticle assay for cardiac
troponin I demonstrated the ability to detect pg/mL con-
centrations of the protein in serum, revealing a significant
increase of the sensitivity of detection and providing a
promising earlier detection of myocardial injury [55].
Using engineered viral nanoparticles combining troponin
antibodies and nickel nanohairs, a different study reported
a detection limit of troponin in human serum with 6–7
orders of magnitude lower than conventional immunoas-
says [56].
In-vivo sensors for CVDs
Myocardial ischemia is the deadliest form of CVD. It affects
millions of people and causes many fatalities. Several
studies have focused on the development of nanosensors
for in-situ rapid detection of ions such as K+, H+, Na+ and
Ca2+ and demonstrated the role of the activity of K+ and H+
ions as potential indicators of the onset of AMI [57]. The in-
vivo analysis was conducted using epicardial and arterial
Review
implantation of sensors. Flexible nanoelectrode sensors for
K+ were also developed to address the mechanism of
ischemic heart disease [58]. In addition, a multi-nanosen-
sor silicon needle was developed in vitro for the detection of
myocardial ischemia during cardiac surgery by employing
field effect transistors (FET) [59]. Nanosensors were also
developed for the in-vitro detection and analysis of real-
time sodium concentration during action potentials [60] in
HEK PN1 cells. The flux of Na+ ions across the cell mem-
brane plays a fundamental part in the generation of action
potentials and regulation of membrane excitability in cells
such as cardiomyocytes. Diseases such as long QT syn-
drome and heart failure have been correlated to an altera-
tion of sodium-channel function. Functionalized nanowires
were developed for real-time detection of Ca2+ ions import-
ant in the context of CVDs [49]. Ca2+ ions are known for
activating biological process such as muscle contraction,
protein secretion, cell death and cell development.
Nanosensors for the detection of other molecules which
play an important part in the physiology of the cardiovas-
cular system are also in development (Table 3). Near-
infrared fluorescence sensors for nitric oxide (NO) were
developed with single-walled carbon nanotube technology
[61]. A porphyrinic nanosensor for in-situ measurement of
NO in endothelial cells or in the beating heart allowed
understanding the effect of hypertension and ischemia–
reperfusion on NO release [62]. In2O3 nanowire-based FET
sensors were employed as lab-on-a-chip devices for detec-
tion of oxidized low-density lipoprotein (oxLDL) cholesterol
[63], which is considered to be a biomarker for acute heart
attack in patients with coronary artery disease (CAD).
Other studies have explored the employment of
nanotechnology for monitoring physical–mechanical
parameters such as pressure and blood flow as potential
CVD indices.
Many bio-MEMS pressure sensors have been developed
in-vitro for the in-situ measurement of blood pressure [64].
These include an implantable device for telemetric real-
time monitoring of blood pressure with the potential to
diagnose myocardial infarction [65]. Additionally, wireless
bio-MEMs sensors for continuous monitoring of blood flow
in-situ reveal opportunities for surveillance strategies to
detect stenosis and to prevent impending graft failure.
Nanotechnology for therapeutic and tissue-
regeneration devices
The utility offered by nanotechnology for cardiovascular
device applications is being primarily investigated as an
Table 3. Nanotechnology based on in-vivo CVD sensors
Sensor targets Technology
K+, H+ ions Field effect transistor (FET)
Na+ ions Fluorescent nanosensors
Ca2+ ions Boron-doped silicon nanowires (SiNWs)
Nitric oxide Single-walled carbon nanotube (SWNT)
oxLDL Cholesterol Porphyrinic nanosensor
Blood pressure In2O3 nanowire-based FET
Piezoelectric-BioMEMS
Chip-embedded flexible packaging (CEFP)
Blood flow Piezoelectric-BioMEMS
oxLDL: oxidized low-density lipoprotein; BioMEMS: BIO-micro-electro-mechanical system.
Trends in Pharmacological Sciences Vol.31 No.5
enhancement of stent technology. The integration of nano-
technology into stent design has provided novel strategies
for drug delivery from mesoporous substrates and
enhanced biocompatibility from nano-textured surfaces.
The classical challenges of deploying stents in an attempt
to revascularize arteries narrowed by disease are in-stent
restenosis as the result of intimal hyperplasia [66], and
late-stage thrombosis mediated by activated platelets [67].
When clinical advancements were thought to be exhausted
through variations of stent geometry, the next degree of
device sophistication established the stent as a drug-deliv-
ery platform. Industry giants such as Boston Scientific,
Johnson & Johnson, Medtronic, and Guidant began man-
ufacturing drug-eluting stents (DESs) that released drugs
such as paclitaxel and sirolimus to exploit their anti-pro-
liferative effects. DESs have demonstrated a lower inci-
dence of restenosis 6 months post-procedure compared
with their bare-metal counterparts, but recent longer-term
studies have raised major concerns over the long-term
benefit of DESs [68–71]. The anti-proliferative nature of
the eluted drugs inhibit the cell cycle, thereby prohibiting
normal vessel remodeling that results in the integration of
the stent within the vessel wall. The exposed structure of
the stent as a result of incomplete neointimal coverage
facilitates thrombus formation, which leads to increased
mortality due to late-stage thrombosis [69]. This outcome
is commonly observed after early cessation of dual anti-
platelet therapy (aspirin/clopidogrel) [70].
In light of the challenges of DESs, nanotechnology is
being applied to stent design to improve outcomes. Nano-
porous platforms have demonstrated the ability to provide
controlled drug-release profiles over a predetermined
period; such nanoporous technology has been applied to
cancer applications [4]. Investigators are exploring the
utility of nanoporous stent surfaces of: aluminum oxide
to deliver tacrolimus [72], carbon–carbon nanoparticle
matrices for the elution of paclitaxel [73], gold [74] or
titanium oxide[75] for the delivery of various therapies.
To ameliorate the problem of impaired revascularization of
vessels mediated by the physical presence of stents, surface
nano-texturing is being investigated to enhance the inter-
action of endothelial cells with stent surfaces. Studies
suggest that nanoscale roughness/topography on nickel
titanium [67] and hydroxyapatite [76] substrates may
mimic the natural structure of vascular tissue and improve
cell adhesion; this will subsequently enhance endothelia-
lization of stent struts and articulations for the reduction of
thrombosis [77]. The next evolutionary stent advancement
Applications Refs
Myocardial ischemia [57–59]
QT syndrome, heart failure
Multiple CVDs
Hypertension Ischemia/reperfusion [60]
[49]
Acute heart attack [61]
Pressure monitoring, [62]
Myocardial infarction [63]
Stenosis in heart bypass Grafts [64]
[65]
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Review
may be realized through a combinatory integration of
nano-porous stent surfaces for the controlled time release
of anti-proliferative agents with nanotextured features.
This will promote vessel endothelialization to lower the
incidence of restenosis and occurrence of late-stage
mortality attributed to thrombosis.
Conclusions and perspectives
In ‘developed’ countries, CVDs represent an enormous
burden on the healthcare system and economy because
they are the leading cause of morbidity and mortality. This
becomes even more important considering the increasing
older and obese population. Rapid evolution in genetics,
proteomics, molecular and cellular biology, material
science and bioengineering, make nanotechnology, which
bridges the gap between interactions on the molecular and
microscopic levels, one of the major potential players in the
progress of the treatment and detection of CVDs. Though
still in the very early developmental stages, cardiovascular
nanomedicine is likely to meet the high demand for break-
through innovation in the diagnosis and treatment of
CVDs. Different from conventional molecular thera-
peutics, nanomedicine enables the design of multi-com-
ponent, multi-tasking, multi-modular agents that can
simultaneously and precisely detect and treat disease.
For example, we can envision smart nano-sensors inte-
grated in existing implants such as defibrillators, stents or
pacemakers that may trigger warnings, or perhaps acute
release of drug, if required. Another nanomedicine solution
for CVDs could be projected for vulnerable plaques; ‘click
chemistry’ or highly controlled cross-linking strategies
targeting and ‘securing’ the plaque before subsequent
AMI without danger of occluding the vessel could be uti-
lized.
In summary, we gave a brief overview on the current
developments in cardiovascular nanomedicine, but we
believe that these pale into comparison with future oppor-
tunities for the application of nanotechnology for the diag-
nosis and treatment of CVDs.
Acknowledgments
Matt Landry is gratefully recognized for his artistry in the preparation of
Figure 1. The authors acknowledge financial support from the following
sources: DODW81XWH-09-1-0212, DODW81XWH-07-2-0101; NASA
NNJ06HE06A; NIH RO1CA128797, NIH – R33 CA122864, NIH
U54CA143837 and State of Texas, Emerging Technology Fund and by
the grant-awarding organizations: Department of Defense (DoD),
National Institutes Health (NIH) and National Aeronautics and Space
Administration (NASA).
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