Advances in nanotechnological approaches for the detection of early markers associated with severe cardiac ailments

Abstract

Mortality from cardiovascular disease (CVD) accounts for over 30% of all deaths globally, necessitating reliable diagnostic tools. Prompt identification and precise diagnosis are critical for effective personalized treatment. Nanotechnology offers promising applications in diagnostics, biosensing and drug delivery for prevalent cardiovascular diseases. Its integration into cardiovascular care enhances diagnostic accuracy, enabling early intervention and tailored treatment plans. By leveraging nanoscale innovations, healthcare professionals can address the complexities of CVD progression and customize interventions based on individual patient needs. Ongoing advancements in nanotechnology continue to shape the landscape of cardiovascular medicine, offering potential for improved patient outcomes and reduced mortality rates from these pervasive diseases.

Plain language summary

Article highlights.

Nanotechnology in early cardiac marker detection

• Nanoparticles possess a wide range of capabilities for diagnostic purposes, namely in the realm of early identification of atherosclerosis by the quantification of inflammatory markers.

• Precision and effectiveness are essential for the detection of heart-type fatty acid-binding protein (H-FABP) as an early biomarker for cardiac events.

• Several techniques, such as chromatography (HPLC, GC-MS) and immunoassays (ELISA, LFIA), can be used with distinct advantages in terms of sensitivity, specificity and turnaround time.

• Challenges with immunoassays include the occurrence of cross-reactivity and interference, while chromatographic procedures require specialized equipment and skilled personnel.

• MicroRNAs (miRNAs) control gene expression and exhibit stability in human fluids, rendering them valuable as biomarkers.

• miRNA-21 is a biomarker that is specifically intriguing for heart failure due to its involvement in both the etiology and diagnostics of the condition.

• Therapeutic approaches aimed at miRNA-21 entail the use of antagomiRs and miRNA mimics, which present opportunities for precision medicine.

• miRNA-21 is involved in heart hypertrophy, fibrosis and remodeling, and its abnormal regulation offers diagnostic and prognostic information.

Current challenges & limitations in early detection

• Early diagnosis of heart issues is essential for effective treatment and better outcomes.

• Advanced cardiac implantable electronic devices (CIEDs) are increasingly employed for congestive heart failure, ventricular tachyarrhythmia and bradyarrhythmia.

• Regular battery changes remain necessary, despite breakthroughs in battery design and CIED programming, resulting in cost, risk and inconvenience.

• Transvenous lead extraction for damaged leads is potentially fatal.

• Spin-echo (SE) sequences, enhanced by ECG-gating, improve myocardial-blood contrast but have limited temporal resolution and motion-related artefacts.

• Ejection fraction (EF), a typical systolic function measure, is susceptible to inaccuracies due to subjective endocardial boundary tracing.

• Emerging biochemical diagnostics for heart disease encounter hurdles in standardization, preanalytical variability and imprecision.

• Reliable economic evaluations of test costs and benefits are lacking.

• Immunoassays for novel cardiac proteins use antibodies targeting various epitopes, resulting in varying results and interpretation challenges.

• “Sandwich” immunoassays may produce false positives due to disturbances in antigen-antibody reactions and interference by factors like rheumatoid factor or human antimouse antibodies.

• The presence of endogenous substances like hemoglobin and bilirubin can lower the sensitivity and specificity of troponin assays.

• POC devices for cardiac troponins and BNP detection are sensitive yet expensive and time-consuming.

Recent advances & innovations in early detection

• Patenting theranostic nanoparticles, developing a UV-cross-linkable cardiac patch with gold nano-rods and creating nanoparticle-based stem cell conjugates for post-infarction treatment are significant advances in spatially designed nanoparticle trials in CVDs, neurological disorders and cancer therapies.

• AuNPs and iron oxide nanoparticles improve imaging of atherosclerotic plaques and CVDs, with CNA35-AuNPs found to improve contrast and detection in CT images.

• MRI, utilizing T2 and T1 mapping, 4D flow imaging and nanoplatforms, enhances imaging accuracy and precision, replacing biopsies for heart structure, function and tissue characteristics.

• PET imaging in CVDs uses radioactive tracers for 3D imaging of biological processes, such as myocardial perfusion using 13N-ammonia, enhanced by nanoplatforms and targeting ligands improving specificity and effectiveness.

• Enhanced ultrasound imaging with nanoparticles targeting vascular markers enhances echogenicity and contrast-to-noise ratio, resulting in safe and effective real-time imaging.

• MSOT and PAI use photoacoustic imaging for high-resolution carotid artery and atherosclerosis detection, with nanoparticles improving sensitivity, contrast and specificity.

• MPI, a real-time, high-resolution imaging method, enhances signal strength and accuracy with optimized nanoparticles for tracer detection, multiplexed imaging and sensitivity.

1. Background

Cardiac markers are substances present in the bloodstream that might serve as indicators of injury or harm to the heart muscle [1]. Timely identification of cardiac markers is needed for the diagnosis and treatment of acute coronary syndrome (ACS), which encompasses acute myocardial infarction (AMI) [2]. According to Braunwald, the connection between coronary thrombosis, myocardial necrosis and the clinical conditions like AMI was not well understood until the early 1900s. Coronary thrombosis, although identified as a cause of death throughout the 19th century, was previously regarded as a medical anomaly [3]. Over time, different biomarkers have been utilized for the identification of cardiac diseases, with cardiac troponins being the most widely recognized indicators for diagnosing damage to the heart muscle [4].

The importance of early identification of cardiac markers include enabling prompt action, thereby mitigating the likelihood of complications and enhancing patient outcomes [2]. Additionally, it could aid in identifying individuals at a greater risk for cardiac events, enabling the implementation of more individualized therapy and management approaches [5]. Biomarkers, such as brain natriuretic peptide (BNP), cardiac troponins and C-reactive protein (CRP), are key indicators of cardiac health and function [6]. BNP indicates cardiac strain and volume overload, but cardiac troponins indicate myocardial damage. Cardiovascular risk may be evaluated with the use of CRP, an indicator of inflammation. Cardiovascular medicine relies heavily on these indicators for risk assessment, prognosis evaluation and therapy optimization [6]. In both clinical and forensic contexts, examining biomarkers such as BNP and NT-proBNP is essential for the diagnosis of cardiac dysfunction [7]. These biomarkers are essential in providing prognostic information for the early identification and treatment of heart failure [7]. Since their levels rise in response to myocardial ischemia and ventricular wall stress, BNP and NT-proBNP have developed into crucial diagnostic tools. It is critical to predict future cardiovascular events based on the history of such events or the existence of pre-existing cardiovascular disease. In the end, effective and ongoing observation of these people may be able to halt or reverse the epidemic of cardiovascular disease [7]. In addition to offering insights into the application of biomarkers for better patient outcomes and clinical decision-making, Santhanakrishnan et al. emphasize the importance of predictive biomarkers for the early identification and treatment of heart failure. The authors stress the need for more study to create automated, objective algorithms that use cutting-edge computational methods, such machine learning, to assess high amounts of multidimensional, high-dimensional data. It is anticipated that in the future, the diagnosis of cardiovascular diseases will be significantly more precise and effective thanks to these algorithms [8].

Cardiovascular disease accounts for almost 30% of global mortality, surpassing cancer in terms of prevalence. Similarly, statistics from the World Health Organization indicate that cardiovascular diseases have accounted for a significant amount [9]. The primary factors contributing to heart diseases are atherosclerosis, smoking, elevated cholesterol levels, obesity, diabetes mellitus, depression and notably, insufficient physical exercise. Wearable devices and sensors are commonly employed to measure and examine blood pressure and hemodynamic fluctuations. They have a key role in the prevention, early identification and management of cardiovascular and neurological disorders [10]. The advent of a consumer-driven health era has arrived, bringing significant potential benefits in the early detection, treatment and management of cardiovascular disease [11]. There are carbohydrate, protein and lipid based biomarkers that are used in early detection, for example Glycogen phosphorylase BB(GPBB) a carbohydrate based marker is used in early detection of cardiovascular diseases [12], Lactate dehydrogenase(LDH) is a protein based biomarker [13] and MicroRNAs (miRNAs) are lipid based markers used in early detection [14]. Early cardiac markers are linked to various conditions, including ACS. ACS is characterized by a sudden decrease in blood flow to the heart muscle, resulting in symptoms such as chest discomfort, pressure, nausea and/or shortness of breath. Another example is myocardial infarction (MI), a form of ACS that occurs when a section of the heart muscle dies because it is not receiving enough blood [2]. Some other examples include myocardial ischemia, myocardial stress and inflammation.

The scientific community faces a significant challenge in developing new approaches to manage vascular diseases, particularly notable due to the limitations of conventional therapy methods involving delivering drug molecules via various methods such as angioplasty, atherectomy, stenting and bypass grafting [15]. Nanotechnology is not only being explored in the investigation of many diseases but also holds great potential as a subject of study in cardiology, with the ability to potentially transform the management and treatment of CVDs [16]. Beneficial advancements can be found in four main areas of nanotechnology: diagnostics, molecular imaging, targeted drug delivery and tissue engineering. The advantages encompass optimized drug delivery to targeted regions, increased drug release and bioavailability and enhanced treatment efficacy accompanied by minimal adverse effects [17,18], as illustrated in Figure 1.

Figure 1.

Cardiovascular diseases their risk factors and their treatments within the nantotechnology platform. Adapted from Shi, C., et al., Nanoscale technologies in highly sensitive diagnosis of cardiovascular diseases.With permission from [91] under the terms and conditions of the Creative Commons Attribution License (CC BY).

Copyright^© 2020 Shi, Xie, Ma, Yang and Zhang.

2. Nanotechnology in early cardiac marker detection

Accuracy and efficiency are necessary for the detection of heart-type fatty acid-binding protein (H-FABP), an early biomarker that is released into the serum within an hour following a cardiac event [19]. To precisely detect and measure H-FABP, a number of approaches have been developed. These methods cover a wide range of approaches, including chromatographic methods like high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS), as well as immunoassays like enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay (LFIA). H-FABP levels in blood samples may be quickly and accurately detected with the use of several methods, each of which has unique benefits in terms of sensitivity, specificity and turnaround time [20]. It is important to recognize the limitations and challenges linked to these methodologies. The accuracy of H-FABP detection in immunoassays can be impacted by cross-reactivity and interference problems. Despite being very sensitive and specific, chromatographic procedures are not widely used in clinical settings since they frequently need for specialized equipment and trained staff. Furthermore, the identification and treatment of cardiac events may be delayed by the lengthier turnaround times associated with these procedures [21].

Moreover, Small non-coding RNA molecules known as micro-RNAs (miRNAs) are essential for controlling gene expression. The stability and presence of miRNAs in bodily fluids have made them attractive biomarkers for a range of disorders. Of these, miRNA-21 has attracted the most interest as a potential biomarker for heart failure. Recent developments about miRNA-21 highlight its importance in the pathophysiology and diagnostics of the heart [22]. Targeting miRNA-21 in heart failure has been studied recently for its therapeutic implications as well as its diagnostic potential. Modulating miRNA-21 levels using strategies like antagomiRs and miRNA mimics has opened up new possibilities for precision medicine techniques in the treatment of heart failure. Furthermore, new research highlights the complex function that miRNA-21 plays in the evolution of heart failure by indicating that it may be transferred via extracellular vesicles and used in intercellular communication within the cardiac milieu [23].

Research has clarified the function of miRNA-21 in heart failure and shown that it is involved in cardiac hypertrophy, fibrosis and remodeling. The dysregulation of miRNA-21 expression in heart failure patients has been brought to light by recent study, offering new perspectives on the diagnostic and prognostic potential of this gene. Furthermore, the identification of miRNA-21 targets and signaling pathways associated in the etiology of heart failure has been made easier by developments in high-throughput sequencing technology and bioinformatics tools.

Novel strategies like nanotechnology provide encouraging ways to get beyond these restrictions. Techniques based on nanotechnology make use of nanomaterials and nanodevices to improve the speed, sensitivity and specificity of the detection of cardiac markers [24].

Nanoparticles offer great versatility in diagnostic applications for CVD due to their ability to be tailored for specific pathological locations and their detectability. An example of a potential use for nanoparticles is the early identification of atherosclerosis, a primary contributor to heart attacks and strokes, through the measurement of inflammatory levels [25], recent studies carried out n this area is mentioned in Supplementary Table S1. Nanoplatforms act as contrasting agents in computed tomography (CT) imaging, enhancing the differentiation between tissue types and simplifying the process of visualizing and diagnosing specific diseases [26,27]. Ultrasound imaging, a secure and straightforward medical imaging technology, has seen recent advancements in nanotechnology with the development of nano-ultrasound imaging materials capable of targeting specific markers related cardiovascular system [28].

2.1. Nanoparticles for sensitive detection

Nanoparticles possess beneficial properties for detection, including higher reactivity, enhanced electrical conductivity, robustness, distinctive magnetic properties and a substantial surface area to volume ratio. Nanosensors utilize the unique optical characteristics of nanoparticles to provide greatly amplified signals, enabling the early identification of diseases [29]. The following nanoparticles are often used for sensitive detection, illustrated in Figure 2.

Figure 2.

Some of the nanoparticles which are being used in CVD cure.

2.1.1. Gold nanoparticles

The utilization of gold for medicinal purposes can be traced back to ancient times in China and Egypt [30]. However, in the recent years, there has been significant interest in the use of gold nanoparticles (GNPs) in healthcare. These nanoparticles have potential applications not only for therapeutic purposes but also as contrast agents in medical imaging. Multiple factors contribute to the high interest in using GNPs in medicine. First, GNPs are easy to produce using various methods, such as chemical, thermal, electrochemical and sonochemical ones [31]. Consequently, GNPs of different shapes [32], ranging in size from 1 to 500 nm, have been produced [30]. Furthermore, GNPs exhibit inert properties, are biocompatible and can be readily customized for precise targeting [33]. Some applications of GNPs in cardiovascular optical includes Photoacoustic Imaging(PAI) [34]. PAI has two configurations: photoacoustic tomography (PAT) for centimeter-depth imaging and photoacoustic microscopy, both utilizing contrast agents like Indocyanine green (ICG) or GNPs for better tissue identification [35–38]. Additionally, GNPs have been evaluated for label-free sensing and detection at the single-molecule level, showing promise in detecting atherosclerotic plaques [39–42].

2.1.2. Quantum dots

The quantum dot immunofluorescence immunoassay employs a two-antibody sandwich technique offering benefits for pre-hospital first aid and early diagnosis [43]. Graphene quantum dots (GQDs) have shown promise in the early detection of cardiac markers, particularly for electrochemical detection of cardiac troponin I (cTnI), a biomarker for for early diagnosis of acute myocardial infarction (AMI) [44–47]. These studies collectively demonstrate the effectiveness of GQDs in the early identification of cardiac markers, showcasing their sensitivity, stability and label-free detection capabilities

2.1.3. Magnetic nanoparticles

Magnetic nanoparticles (MNP) are contributing to the field of cardiovascular molecular imaging in an increasingly significant way. The core of these agents is made up of iron oxide, and they are superparamagnetic. They are wrapped by a coat of carbohydrate or polymer. MNP are ideally suited for cellular and molecular imaging of atherosclerotic plaque and cardiac damage due to their size, physical characteristics and pharmacokinetics [48]. MNP are usually superparamagnetic, but they can be made to be ferromagnetic or paramagnetic, which aren't very good for MR imaging [49]. There are two ways in which molecular MR agents can be directed toward a particular target. An affinity ligand, which can be an antibody, fragment, protein, peptide, or apatamer, is attached to the surface of the cell in order to target a specific protein or molecule, such as the αvβ3 integrin [50], phosphatidylserine [51], or VCAM-1 [52]. The second strategy is to alter the MNP uptake by modifying its surface with tiny molecules [53]. MNP imaging has been utilized to visualize molecular targets in conditions such as atherosclerosis, cardiac damage and stem cell treatment [54,55]. The study presented a novel method called magnetic nanochains-based dynamic ELISA, which enables fast and highly sensitive identification of biomarkers for acute myocardial infarction. This study showcased the capability of magnetic nanoparticles to improve the accuracy and efficiency of identifying cardiac markers, namely in the case of AMI [56]. A number of studies have been carried out to identify biomarkers by the utilization of MNP, hence highlighting their potential in the early detection of cardiac markers, such as CTnI, for the early diagnosis of AMI [57].

2.2. Nanowires & nanotubes for rapid analysis

In recent years, nanofiber structures have gained increasing appeal due to their numerous advantages, particularly the enhanced reaction rate and sensitivity of biosensors resulting from the large surface area of nanofiber structures [58], illustrated in Figure 3. Nanowires and nanotubes are being extensively studied for various applications in the context of CVDs. Carbon nanotubes, silicon nanowires and zinc oxide nanowires are some of the materials that are being investigated for this purpose.

Figure 3.

illustrated the recent advances in the development of nanowire based sensing device.

2.2.1. Carbon nanotubes

Carbon nanotubes (CNTs) exhibit extraordinary mechanical strength, electrical conductivity and chemical behavior making them highly promising materials for various applications, including cardiac constructions [59]. One significant advantage of CNTs in cardiac tissue engineering is their intrinsic shape and anisotropic mechanical and electrical capabilities, which facilitate the alignment of electroactive cardiac cells in a single direction, simulating the anisotropic alignment of cardiomycocytes found in heart tissue [60]. Their uses in medication delivery, biosensors, tissue engineering and immunomodulation for cardiovascular disorders has been highlighted in numerous studies [61].

For instance, a study demonstrated the selection and utilization of fluorescent single-walled CNTs s for detecting microRNA biomarkers associated with acute AMI [62]. Additionally, a label-free biosensor utilizing carbon nanofiber (CNF) nanoelectrode arrays was developed for detecting cardiac Troponin-I, a key biomarker for early cardiac injury. The results of this investigation underscores the potential of carbon nanofibers for sensitive and specific detection of cardiac biomarkers [63].

2.2.2. Silicon nanowires

Silicon nanowire field-effect-transistors (Si-NW FETs) are currently undergoing extensive study as highly effective a highly effective diagnostic tool due to their ability to detect with extreme sensitivity, selectivity and in RT without the need for labeling [64]. These advantages stem from their operational concept, which relies on the gating effect of the antigen–antibody binding interactions occurring on the surface of the NW. Moreover, Si-NW FETs offer several benefits, including easy integration with signal processing circuits, low costs and little device-to-device variation. This is due to the fact that these devices can be manufactured using commercial microfabrication techniques [65].

A critical biomarker for acute myocardial infarction is cTnI, a protein released into the bloodstream following injury to the heart muscle. cTnI detection has led to the development of SiNW field-effect transistors (SiNW-FETs). These devices operate by immobilizing cTnI-specific antibodies on the surface of SiNW. When antibodies bind cTnI, it alters the electrical characteristics of the SiNW and the device's current flow. A label-free and extremely sensitive readout of cTnI concentration can be obtained by measuring this change in real-time [66]. By incorporating specific antibodies to SiNW arrays, it becomes feasible to detect numerous cardiac indicators, enabling early detection of cardiac events and a more comprehensive assessment of heart health. For instance, one study achieved highly specific detection of three indicators simultaneously using SiNWs functionalized with antibodies against cTnl, myoglobin and CK-MB [67].

2.2.3. Zinc oxide nanowires

Zinc oxide (ZnO) is an inorganic compound classified under the II-VI group of semiconductors. In the region of the ultraviolet (UV) spectrum, it exhibits a rather wide band gap of 3.37 eV. Additionally, it possesses a significant exciton binding energy of 60 meV at normal temperature [68]. The hexagonal wurtzite structure is the most thermodynamically stable form of ZnO under normal conditions of environmental pressure and temperature, despite the fact that it can crystallize in three other forms: zinc blende, wurtzite and rocksalt [69].

Both ionic and semiconducting properties of ZnO have the potential to contribute to the appropriate level of sensitivity when it comes to the detection of target biomarkers at extremely low concentrations. Furthermore, this specific metal oxide may be cultivated as nanostructures using current manufacturing techniques that can be easily scaled in terms of volume, all while maintaining a low cost of ownership [70,71].

In a study, a sensor platform was developed using ZnO nanorods to detect cTnT via an electrical/electrochemical transduction process [72]. ZnO nanorods, synthesized through a hydrothermal technique served as the immobilization matrix for antibody capture. The density, aspect ratio and crystalline structure of the ZnO nanorods are among the factors influencing the electrochemical performance of the ZnO nanobiosensor. The study demonstrate the correlation between the density of ZnO nanorods and the resilience of the electrodes [72].

Another study developed an AMI sensor using ZnO nanoparticles doped with chromium. Within three hours following the onset of AMI symptoms, there is a notable increase in myoglobin levels, which serves as a crucial early indicator. Early measurement of myoglobin levels is essential for preventing AMI-associated complications. ZnO nanoparticles offer efficient and precise techniques for detecting myoglobin, enabling early identification and confirmation of AMI [73].

Furthermore, ZnO have been integrated into paper-based fluorogenic immunodevices to amplify the detection of several cardiac biomarkers, including cTnI, human heart-type fatty acid binding protein (FABP) and myoglobin. This application underscores the ability of ZnO nanowires to amplify fluorescence signals for the identification of these biomarkers [74]. The use of ZnO nanowires has demonstrated significant potential in the preliminary identification of cardiac biomarkers. Apart from pre-concentration, sensor fabrication, fluorescence signal enhancement and biosensor development, they have been implemented in a variety of other applications.

2.3. Nanoscale biosensors for specific marker identification

The development of biosensor aims to provide a means for detecting and quantifying certain chemicals. A powerful analytical tool, it finds widespread use in medical diagnostics [75], illustrated in Figure 4. This involves the identification of proteins, detection of nucleic acids and examination of antibody-antigen interactions. Typically, a transducer surface is used to immobilize a receptor material like DNA, antibody, or RNA which then converts the biochemical signal into measurable electrical impulses. Various measuring devices has been developed to detect CVD indicators [76].

Figure 4.

Some of the nanoscale biosensors used in CVD cure.

2.3.1. Optical biosensors

Optical biosensors detect biorecognition processes by monitoring changes in the phase, amplitude, polarization, or frequency of the input light, making them among the most sensitive techniques. These biosensors can be categorized as, colorimetric, fluorescence, luminescence, bio-optrode-based biosensors and surface plasma resonance (SPR) biosensors [77].

For the early detection of cardiac biomarkers, luminescence-based biosensing platforms and methodologies have recently been investigated [78,79]. There are two main categories of luminescence techniques: chemiluminescence and electroluminescence. Researchers have not yet thoroughly investigated electroluminescence (ECL) and colorimetric biosensing platforms cardiac marker detection via biosensing platforms. Using self-assembly and gold nanoparticle amplification techniques, a new label-free ECL biosensor for the detection of low-density lipoprotein (LDL) has been devised, based on the ECL of CdS nanocrystals [80].

Their vulnerability to background noise interference is a major drawback that may compromise measurement accuracy. Furthermore, the operation and accessibility of optical biosensors for point-of-care applications are limited due to the need for expensive apparatus and expertise. Furthermore, especially in environments with limited resources, the expense of optical biosensor technology may make it unfeasible for broad use [81].

The SPR technique depends on measuring the refractive index of extremely thin layers of material that are adsorbed onto a metal surface. In SPR immunosensing, antibodies are fixed onto the surface of a thin metal film, typically gold-coated onto the reflective surface of a glass prism [82]. Numerous studies and applications of SPR-based sensing platforms have focused on the detecting of cardiac makers including matrix metalloproteinase (MMP)-2, C-reactive protein (CRP), B-type natriuretic peptide (BNP) and cTnT [83].

To measure MMP-2 in a single step, one approach uses a sandwich assay format based on surface plasmon resonance (SPR). Similarly, a signal amplifier made of colloidal gold particles (about 20 nm in diameter) is employed [83]. The cTnT was detected using a sensor device that was built on carboxymethyldextran hydrogel [84]. To increase the number of immobilised antibodies, a study utilised the widely recognised biotin-streptavidin chemistry, which involves a highly selective interaction between the biomolecules [85]. There have also been reports of other refractive index-based optical biosensors, such as a resonant biosensor for CRP indicator detection and silicon photonic microring resonators incorporated into an optofluidic platform for IL-6 detection [86]. These biosensors have been utilized for detection of cardiac troponin including cTnT and I [87]. Because of its simple design and excellent analytical performance, the use of magnetic particles for optomagnetic detection of cardiac biomarkers offers a novel approach to point-of-care diagnostics [88].

2.3.2. DNA nanosensors

DNA nanosensors are capable of detecting cardiac markers at an early stage. Nanosensors can be engineered to selectively capture target biomolecules, such as proteins, and accurately detect them even at extremely low levels. A particular example of a cardiac biomarker that can be identified through the use of DNA nanosensors is C-reactive protein (CRP) [89].

Nanotechnology offers numerous advantages in detecting molecular and cellular biomarkers associated with CVDs. Nanomaterials can be integrated into the “ink” used in 3D bioprinters to mimic the intricate, contractile, conductive and thermal properties of the human heart [90]. DNA nanosensors can be incorporated various platforms, including electrochemical, fluorescence, surface-enhanced Raman scattering (SERS) and enzyme-linked immunosorbent assay (ELISA). These platforms have the potential to enhance the sensitivity and accuracy of cardiac biomarker identification, making them suitable for the diagnosing of CVDs in its early stages [91].

Even with their great sensitivity and specificity, DNA nanosensors have stability and repeatability issues. DNA nanosensors can be complicated and variable in their production and functionalization, which compromises their suitability for routine clinical application. Moreover, the incorporation of DNA nanosensors into diverse detection platforms would necessitate specific tools and knowledge, which could hinder their extensive use [92].

2.3.3. Aptamer-based sensors

Aptamer-based sensors have become a highly promising means of the early identification of cardiac markers. These markers have a main role in the diagnosis, prognosis and estimation of risk associated with CVDs. Aptamers are short molecules composed of a single strand of DNA or RNA with the ability to bind to specific target molecules with a high affinity and specificity, which makes them an attractive alternative to antibodies for analytical applications [93].

An effective approach for creating aptamer based sensors that detect cardiac biomarkers involves the use of electrochemical biosensors. These sensors have exhibited excellent analytical capabilities in detecting cardiac biomarkers, such as, BNP-32 and cTnI, which are widely used in diagnosing cardiovascular disorders [94]. Screen-printed electrodes have shown promising outcomes in detecting biomarkers through the use of reusable electrochemical aptasensors [95]. Cardiac troponin is considered the most reliable and accurate cardiac biomarker for diagnosing damage to the heart muscle, particularly in cases of myocardial infarction (MI). Its high specificity and selectivity make it a commonly used tool for early MI detection. In a study, molybdenum disulfide (MoS2) nanosheets, ranging from 200 to 400 nm, in conjunction with an aptamer to create a TnI aptasensor [96]. This aptasensor uses a conjugated aptamer-MoS2 nanosheet-modified glassy carbon electrode as the transducer. After coating MoS2 nanosheets on the working electrode, a TnI high-affinity aptamer was conjugated. Most aptamer based strands caught TnI with great affinity and released from MoS2 nanosheets in presence of TnI, but in the absence of those molecules, they were stable and conjugated. The impedance variations for bound and unbound aptasensor with TnI permitted quantitative TnI determination. The aptasensor detected TnI from 10 pM to 1 μM with a LOD of 0.95 pM. Gold nanocrystal (gold NC) was electrochemically produced on an ITO-coated glass substrate as the working electrode in another study [97].

Myoglobin (Mb) is a small iron-containing protein with a molecular weight of 17 kDa, responsible for oxygen storage and transport in skeletal and cardiac red muscles. Within the first three hours of MI, Mb is one of the earliest biomarkers. It wasn't until 1975 that researchers found a link between MI and high Mb levels [98]. Using gold nanoparticles coated on boron nitride nanosheets (gold NPs/BNNSs), a Mb aptasensor has been developed [99]. A recent advancement in the field is the development of reagent-free electronic biosensors of directly detecting disease indicators in unprocessed body fluids [100].

Although promising, aptamer-based sensors have drawbacks that must be resolved. Batch-to-batch variability in aptamers can affect sensor performance dependability and consistency. Furthermore, it might take a lot of time and resources to choose and optimize aptamers for certain targets. Additionally, non-specific binding and interference from complex biological materials may provide difficulties for aptamer-based sensors, which may reduce their specificity and accuracy for identifying cardiac biomarkers [101].

2.3.4. Acoustic biosensors

Acoustic biosensor offer a label-free detection method and are commonly used for analyzing binding events involving interleukin proteins and CRP. The identification of these indicators relies on the measurement of the mass of the caught substance by a receptor molecule that is fixed to the surface of the quartz crystal resonator. The relationship between this mass and the resonant frequency is linear [102]. Detection using biosensor platform based on surface acoustic waves has also been demonstrated [102,103]. High sensitivity for interleukin-6 (IL-6) detection has been reported by a ZnO/SiO2/Si Love mode surface acoustic wave (SAW) biosensor. The interleukin family of proteins in human serum could be detected in real time by this sensor, which used fully integrated CMOS Si chips [103].

Even with their great sensitivity and label-free detection capabilities, acoustic biosensors may have issues with sample throughput and multiplexing capacity. Variations in temperature and sample viscosity might impact the acoustic biosensors' sensitivity to detection, resulting in inconsistent results. Furthermore, the complexity and expense of acoustic biosensors may increase if specific production methods and materials are needed [104].

2.3.5. Electrochemical based biosensors

Electrochemical biosensors, the first biosensors that were scientifically proposed and effectively brought into the market to detect various analytes [105]. They use variations in currents and/or voltages at a particular surface in solution to identify target molecules using a static identification element, or probe [106]. Recent advancements introduced electrochemical biosensors capable of detecting cardiac indicators such as cTnI, LDL, CRP, myoglobin and MPO. For instance, myoglobin detection has been achieved using a portable point-of-care sensor utilizing impedimetric sensing to detect cardiac enzymes. This sensor efficiently captures the enzyme because it has an antibody layer and planar gold electrodes [105]. The utilization of nanomaterials in electrochemical biosensors has garnered significant interest from research groups in last decade. Selection of nanomaterials offers a wide range of options to measure the detectable signal that can identify analyte concentrations with great flexibility. A novel sensor utilizing a heterogeneous sandwich immunoassay technique has been recently developed, specifically designed for measuring high sensitivity CRP (hs-CRP). This sensor is disposable, user-friendly and highly sensitive [107].

Although extensively utilized and adaptable, electrochemical-based biosensors have limits that require attention. Electrode fouling is a potential issue for these biosensors, which over time may reduce their sensitivity and accuracy. Furthermore, variables like pH, temperature and sample matrix composition can affect how well electrochemical biosensors work, necessitating rigorous calibration and tuning [108]. Furthermore, the incorporation of nanomaterials into electrochemical biosensors could pose issues with repeatability and scalability, which would impede the devices' ability to be used in real-world clinical settings [109].

2.4. Nanoparticle driven multimodal ELISA for enhanced biomarker detection

A potential method for improving the sensitivity and specificity of biomarker identification in CVDs is nanoparticle-driven multimodal ELISA, which has gained popularity recently. This novel approach overcomes the drawbacks of conventional ELISA techniques by utilizing the special qualities of nanoparticles to enhance signals and enable multimodal detection methodologies [110]. Researchers can detect key indicators of cardiac damage or dysfunction with unprecedented sensitivity by functionalizing nanoparticles with specific capture molecules that target cardiac biomarkers, such as brain natriuretic peptide (BNP), C-reactive protein (CRP), or cardiac troponins [111].

For the identification of biomarkers in cardiac conditions, the incorporation of nanoparticles into the ELISA procedure has a number of unique benefits. First off, the assay's sensitivity is increased and the limit of detection is lowered due to the high surface area-to-volume ratio of nanoparticles, which enables effective biomarker pickup and signal amplification [112]. Furthermore, the adaptability of nanoparticles makes multimodal detection methodologies possible, which permits the simultaneous evaluation of many biomarkers in a single experiment [113]. This capacity is especially important when it comes to CVDs, since evaluating many biomarkers can offer thorough insights into the etiology, prognosis and response to therapy of the disease. Moreover, there is potential for integrating laboratory-based biomarker tests into clinical practice for better patient care through the use of nanoparticle-driven multimodal ELISA. This approach's improved sensitivity and specificity allow for the early identification of cardiac biomarkers, which in turn allows for prompt intervention and risk assessment in patients who are either at risk of or currently experiencing cardiovascular disease. Furthermore, nanoparticle-driven multimodal ELISA's scalability and reliability make it an excellent choice for population-based research and high-throughput screening projects that seek to clarify the epidemiology and etiology of cardiac conditions [114].

3. Current challenges & limitations in early detection

It is necessary to discover cardiac problems at an early stage in order to ensure successful treatment and improved results. The early detection process, on the other hand, comes with a number of difficulties and limitations. The following are some of the challenges such as:

Patients with congestive heart failure, ventricular tachyarrhythmia and bradyarrhythmia now have access to advanced cardiac implantable electronic devices (CIEDs). Their use is significantly increasing due to population shifts and the expanded indications [115]. Despite how excellent these technologies are, restrictions remain. In the future, CIED system interventions such as generator replacement, lead modification and device system update will become increasingly popular as the population ages and life expectancy increases. Technical advancements in battery design and CIED programming have increased battery survival, but regular battery changes are still necessary, which comes with the cost, risk and inconvenience of the process [115,116]. Riata and Sprint Fidelis defibrillator lead advisories are two well-known cases from the last few years. Transvenous lead extraction, a treatment that can have potentially life-threatening complications, might be needed to remove damaged or “advisory” leads that are deeply embedded in cardiac tissue [117].

Initially, the spin-echo (SE) sequence was utilized for the purpose of assessing the morphology of the heart. After the development of ECG-gating, SE techniques became more effective by significantly reducing the amount of motion artifacts [118]. The contrast between the myocardium and the blood is typically improved by SE sequences. The signal void that is produced by flowing blood is the reason why these images are referred to as “black-blood” representations. Blood signal is reduced and contrast is increased on gated SE images when presaturation with radiofrequency (RF) and lowering of the echo time (TE) are administered [119]. despite the fact that it is readily available, Imaging with SE has a limited temporal resolution and is reduced by respiratory and other motion-related aberrations [120]. In clinical practice, EF (ejection fraction) is the most usual way to measure systolic function. There are, however, some problems with it as a way to measure how the left ventricle contracts. Tracing the endocardial borders incorrectly introduces an element of subjectivity into both the subjective visual estimate and the quantitative analysis [121,122]. Some analytical and interpretive issues have arisen as a result of these rapid and substantial advances in the creation of new biochemical tests for cardiac disease [123]. Difficulties arise in test standardization, preanalytical variability and imprecision. Also, there are issues with the turnaround time and the assessment of POCT devices as a potential substitute in specific cases. To date, there has been a lack of reliable economic evaluations that weigh the costs and advantages of the biochemical indicators and look at their effects from a results standpoint [124]. The identification of every new cardiac protein involves the utilization of various immunoassays that employ antibodies that target distinct epitopes present on the respective antigens. Multiple outcomes may be derived from various systems and assay generations; consequently, this issue may obscure the interpretation of reported data [125].

False-positives can occur in “sandwich” immunoassays due to disruptions in the antigen-antibody reaction [126]. Commercial tests may be affected by interference from rheumatoid factor or human antimouse antibodies, posing challenges for clinicians and potentially leading to unnecessary procedures like cardiac catheterization [127,128]. Endogenous chemicals, such hemoglobin and bilirubin, can also negatively or positively affect troponin tests [129]. These interferences can greatly reduce the clinical sensitivity and specificity of the marker in certain circumstances [130]. Several highly effective Point of care (POC) devices capable of detecting cardiac troponins and BNP with strong binding are now available on the market. The most recent assays attain exceptional sensitivity to minimize the occurrence of false negatives. Nevertheless, they still possess disadvantages such as excessive expenses and lengthy processing durations [95].

4. Recent advances & innovations in early detection

Many different types of spatially designed nanoparticles are undergoing testing for potential widespread use in many different industries. This is due to the fact that nanotechnological concepts have been applied to biological problems [131]. The idea of nanotechnology has gained recognition for its potential application in the treatment of CVDs and neurological disorders. This recognition has been particularly strong in the field of cancer therapies [132]. Researchers have come a long way in the past few decades, patenting theranostic nanoparticles with differential formulation as multifunctional biomaterials for a wide range of biological uses. This development may play a key role in the future when it comes to effectively managing cardiovascular disorders and other diseases [114]. The development of new biomaterials for the treatment of CVDs has also made significant progress. A new patent (US20170143871 A1) describes a UV-cross-linkable cardiac patch made of gelatin and methacrylate that is impregnated with gold nano-rods. These rods have superior physicochemical properties, such as a high surface area and better conductivity. The development and patenting of nanoparticle-based stem cell conjugates (JP5495215 B2) for use in the treatment of patients in the post-infarction phase is another recent invention [133].

4.1. Integration of nanotechnology with imaging techniques

4.1.1. Computed tomography

Nanotechnology has demonstrated potential in enhancing the image of atherosclerotic (ASVD) plaques that are cholesterol, lipids and further compounds accumulations that is leading to the increase in the risk of heart attack and stroke. Standard CT imaging may not effectively identify atherosclerotic plaques. However, the utilization of nanoplatforms that precisely target these plaques can improve the accuracy and precision of tomography in early-stage detection CVDs [134]. Several nanoplatforms utilized for CVDs imaging include AuNPs, which possess strong x-ray attenuation that activate easily with targeting molecules to selectively mark atherosclerotic plaques. Also, targeted molecules can be used to modify iron oxide nanoparticles, they have been demonstrated to improve the imaging of myocardial infarction [135]. Researchers conducted a study where they utilized a high-density lipoprotein (HDL) which selectively affects macrophages, known as Au-HDL, along with spectral CT imaging. The purpose was to identify macrophages in the mice's arteries with atherosclerosis and simultaneously capture images of the blood vessels. Apolipoprotein E knockout mice are a well-known model for atherosclerosis and this study's results showed that the spectral CT system effectively detected the accumulation of Au-HDL nanoparticles in the aorta of these animals [136]. The purpose of the study was to use in vitro and in vivo tests to determine how strongly a newly created nano-contrast agent bound to the cardiac necrosis antigen (CNA). The findings showed that CNA35-AuNPs greatly improved the contrast between normal and injured cardiac tissue in CT images. There was also a clear correlation between the degree of contrast enhancement and the seriousness of the cardiac damage. Thus, CNA35-AuNPs hold promise as a noninvasive CT imaging technique for scar burden in the heart [137].

4.1.2. Magnetic resonance imaging

Magnetic resonance imaging (MRI) is now a necessary instrument for assessing CVD. MRI offers detailed visual representations of the heart and its accompanying blood vessels, enabling a noninvasive evaluation of the heart's structure, function and tissue properties. By enabling a more precise evaluation of modifications in tissue composition and the identification of small abnormalities that would go missed with standard imaging techniques, this methodology has the potential to enhance the accuracy of assessment [138]. T2 mapping can identify swelling, inflammation and ischemia; T1 mapping can identify cardiac fibrosis, a key component of numerous cardiomyopathies. Some cardiovascular diseases, like heart failure, myocardial infarction and cardiomyopathies, may be better diagnosed and treated with these techniques. Magnetic resonance imaging (4D flow imaging) is another exciting CVD use of MRI, which visualizes and quantifies heart and great vascular blood flow patterns. 4D flow imaging can reveal CVD hemodynamics like aortic stenosis, coarctation and congenital heart disease [139]. Furthermore, MRI is valuable for providing guidance and monitoring the efficacy of cardiac therapies, including ablation procedures, cardiac resynchronization therapy and device implantation. Utilizing RT MRI assistance can enhance precision,protection of these treatments, resulting in improved outcomes for patients with CVD [140]. For the purpose of giving focused contrast enhancement to certain tissues or cells, nanoplatforms have the capability of enhancing the accuracy and precision of imaging. It is possible to use targeted nanoparticles in order to visualize the endothelial cells that are responsible for the formation of the inner lining of blood vessels. These cells are an essential component in the advancement of atherosclerosis and other vascular diseases [141]. In fact, nanoparticles can be utilized as a viable substitute for conventional biopsy techniques by delivering them to the targeted area and subsequently identifying their location and concentration by MRI. An example of this is when a research team effectively visualized the area of rejection following a rat heart transplant by using a contrast agent particles as dextran-coated ultra-small superparamagnetic iron oxide [142].

4.1.3. Positron emission tomography

One non-intrusive imaging method which uses tiny quantities of radioactive tracers to create three-dimensional pictures of internal biological processes is Positron Emission Tomography (PET). This technique is utilized in CVD in order to assess the circulation of blood, metabolic processes and cellular function in the heart and blood vessels [143]. A prominent application of PET in CVD involves assessing myocardial perfusion, which refers to the circulation of blood to the cardiac muscle. Typically, the process involves the utilization of a radiotracer known as 13N-ammonia, which is absorbed by the cardiac muscle cells in correlation with the amount of blood flow [144]. It has been suggested that nanotechnology could be used to develop advantageous instruments for PET imaging in CVD. Liposomes, dendrimers and nanoparticles are the nanoplatforms that are utilized in the process of PET imaging for cardiovascular disease [145]. Several different targeting ligands, such as aptamers, antibodies, or peptides, have been incorporated into the nanoplatforms in order to enhance their functionality. These ligands have the ability to specifically attach to particular biomarkers or receptors that are excessively expressed in CVD [146]. Nanoplatforms can be used to encapsulate hydrophobic imaging components and to attach chelating agents, allowing for high-affinity binding to various non-radioactive or radioactive heavy metal ions like ¹¹¹In, ⁹⁹mTc, ⁶⁸Gd, ⁶⁷Ga and others commonly used in imaging techniques [132].

4.1.4. Ultasound imaging

A medical imaging method called ultrasound imaging gives pictures in real time and is thought to be safe and easy to use. Recent advancements in nanotechnology have enabled the creation of nano-ultrasound imaging materials capable of selectively targeting certain markers associated with blood vessels [28]. The VEGF receptor 2 (VEGFR2) is the specific target of nanoparticles that have been specifically created for use in vascular ultrasonography. This makes ultrasound pictures of blood vessels in tumors clearer and helps drugs find their way into them [147]. Researchers used ultrasound contrast agent perfluorooctyl bromide for MR and ultrasound pictures of rats with atherosclerosis before and after they were injected with nano capsules [148]. Echogenicity was observed in the targeted group at a level of 65.1 dB when ultrasonic imaging was performed. On the other hand, the nontargeted group and the control group did not exhibit any echogenicity at all (46.7 and 46.0 dB, respectively). The utilization of nano capsules also led to a significant decrease in the contrast-to-noise ratio, which was measured at 74.2, specifically within the group that was being targeted. This was a result of the utilization of nano capsules. In the nontargeted and control groups, which had ratios of 48.9 and 46.9, respectively, there was no evidence of this contrast reduction and it was not observed [148].

4.1.5. Enhancing carotid artery & atherosclerosis imaging with nanoparticles in MSOT & PAI

Since early diagnosis and precise evaluation are essential for reducing the risks associated with cardiovascular events, non-invasive carotid artery imaging and the detection of atherosclerosis constitute important undertakings in cardiovascular medicine [149]. Recent years have seen the emergence of potential methods for high-resolution and sensitive visualization of vascular structures and the characterization of atherosclerotic plaques, including Multispectral Optoacoustic Tomography (MSOT) and Photoacoustic Imaging (PAI) [150]. Furthermore, the capabilities of MSOT and PAI processes have been further improved by the inclusion of NPs, creating new opportunities for increased treatment monitoring and detection in cardiovascular diseases [151].

Using the photoacoustic effect – in which tissue absorbs light energy and produces acoustic waves that can be detected and reconstructed into high-resolution pictures –MSOT and PAI are able to produce images with high resolution [150]. Using laser light at certain wavelengths, MSOT and PAI make endogenous chromophores, such lipids and hemoglobin, visible. This makes it easier to identify vascular structures and classify atherosclerotic plaques according to their optical characteristics [152]. But difficulties like shallow penetration depth and inadequate contrast between healthy and sick tissues have made it difficult to apply MSOT and PAI in clinical settings [153].

These issues are resolved by the addition of NPs to MSOT and PAI, which improves the modalities' sensitivity and contrast. Target tissues produce photoacoustic signals that can be enhanced by using the distinct optical and acoustic characteristics of NPs. In the near-infrared (NIR) range, for example, gold nanoparticles (AuNPs) display significant optical absorption, which allows for deep tissue penetration and selective imaging of the carotid artery and atherosclerotic plaques. In this range, biological tissues show limited absorption and scattering [154]. Additionally, the targeting ligand-functionalized NP surface enables for targeted accumulation inside sick tissues, improving the specificity of PAI and MSOT in identifying and characterizing atherosclerosis. In addition, NPs have the potential to function as molecular imaging contrast agents, allowing the identification of certain molecular markers linked to inflammation and plaque vulnerability. Researchers may identify and track molecular indicators of atherosclerosis, such as matrix metalloproteinases (MMPs) or endothelial adhesion molecules, by conjugating NPs with targeted moieties like antibodies or peptides [155].

4.1.6. Enhancing magnetic particle imaging with nanoparticles for improved biomedical imaging

In biomedical applications, magnetic particle imaging (MPI) has shown promise as a high-resolution, real-time imaging method for tracers-labeled targets. However, by utilizing the special qualities of NPs, MPI's sensitivity and spatial resolution may be further increased. NPs improve tracer detection, multiplexed imaging and targeted imaging of certain biological entities when added to MPI procedures [156]. The magnetic characteristics of NPs allow them to generate a significant signal when exposed to an oscillating magnetic field, making them effective contrast agents in MPI [157]. Comprehensive characterization of intricate biological systems is also made possible by the multiplexed imaging of several targets at once made possible by the adjustable magnetic characteristics of NPs [158]. Furthermore, by optimizing their size, shape, or composition, NPs may be made to display improved magnetic characteristics such higher magnetism or relaxivity. These specially designed NPs increase MPI's sensitivity and signal strength, making it possible to identify low-concentration targets with extreme accuracy [159].

5. Conclusion

To summarize, nanotherapies are rapidly becoming a viable option for the treatment of CVDs. In the near future, nanotechnology-assisted treatments will take the place of conventional invasive cardiology, hence expanding the scope of microtechnology for the diagnosis and treatment of CAD. On the other hand, considerable problems continue to exist because of insufficient and inconsistent delivery. Novel ways to improve the targeted delivery of systemically distributed nanoparticles by changing the particle's physical features or enlisting immune cells as carriers are beneficial to the efficiency of nanotherapeutic interventions in the treatment of cardiovascular and other inflammatory diseases. Further investigation is required to emphasize the utilization of advanced computational techniques, such as machine learning to develop algorithms that are objective and automated for the purpose of analyzing high-dimensional, multidimensional data on a large scale. With the help of these algorithms, the diagnostic process for cardiovascular disorders is expected to become substantially more accurate and efficient in the future.

6. Future perspective

Nanotechnology, a novel scientific field, offers promising opportunities for healthcare professionals to accomplish previously unattainable aims. However, it is important to enhance understanding and expand the applications of nanotechnology. Nanomedicine holds significant promise for the treatment of CAD. Ongoing research is focused on developing efficient nanodrug delivery methods for various types of medications. Nevertheless, there are other challenges associated with implementing these technologies. These include the uncertainty around the age of nanomaterials within biological cells, insufficient knowledge regarding the biological safety of nanoparticles at the cellular level and the potential for direct toxicity within living cells due to their chemical composition. Simultaneously, nanoparticles can potentially induce allergic reactions, inflammation and heightened angiogenic intima within the body [160]. According to some reports, nanomaterials that could be used in biological processes are toxic in different ways, based on where they enter the body (liver, kidneys, skin, brain, heart, etc.) and how they are shaped and chemically made. But there is hope that nanomaterials' harmful effects can be lessened or even eliminated if their surfaces are designed with various biocompatible and nontoxic natural or manmade polymers and other chemicals [161]. In particular, using nanomaterials to engineer heart tissue has a lot of promise for treating CVD. Researchers have looked at different kinds of nanoparticles to see if they can improve the function and growth of cardiomyocytes. For cardiac tissue engineering, these materials have been used to make scaffolds and early tests on animals have shown that they work well. For the purpose of incorporating bioactive chemicals and so fostering increased tissue growth, researchers have utilised these scaffolds [146]. Emerging technologies actually have a lot of opportunities for nanotechnological inclusion and integration. It is believed that wearable cardiac monitors will soon play a more significant role in clinical practice, complementing their current diagnostic uses [162]. For label-free, single-molecule sensing and detection, feedback mechanisms can be developed by making use of the physiochemical features of nanoparticles. These nanoparticles include plasmonic nanomaterials, core-shell nanostructures, nanoarrays and nanoscale gaps [163,164]. The integration of wearable technologies with wireless Bluetooth technology enables continuous health tracking, which is anticipated to facilitate patients in determining the appropriate time to consult their doctors, while also assisting medical personnel in efficiently prioritizing their patients [110]. These advancements are expected to assist in monitoring and retrieval of heart failure. Given that the most influential factor in predicting a future cardiovascular event is the presence of pre-existing CVD or a history of such events, like deep vein thrombosis (DVT), heart attack, or stroke, it is crucial to continuously and effectively monitor these individuals. This monitoring could play a vital role in ultimately stopping or reversing this epidemic [165]. Although nanotechnology has made considerable progress in the diagnosis of cardiovascular diseases, it is still challenging to make an early-stage diagnosis due to the lack of clarity in symptoms and the relatively low expression levels of early-stage cardiac biomarkers, which makes nanotechnological testing especially difficult. The biomarker's sensitivity and specificity are major considerations. An absence of sensitivity and specificity in the diagnosis of CVD may be caused by insufficient single indicators, according to previous studies. It is not feasible to get definitive diagnosis results with a single biomarker because of the ambiguity, diversity and variability of pathophysiology between populations. Biomarkers may also be subject to varied controls as diseases progress [110]. To create automatic and objective algorithms for processing large, complicated data sets, one important area for advancement is the combination of nanotechnology with sophisticated computational methods, such machine learning. The potential exists to improve the precision and efficacy of diagnostic procedures for cardiovascular diseases by leveraging the capabilities of nanotechnology, namely in the creation of imaging innovations and biosensors. Furthermore, a potential option for ongoing health monitoring is provided by wearable cardiac monitors with wireless Bluetooth integration, which helps medical practitioners prioritize patient care while also empowering people to take charge of their cardiovascular health. The field of cardiovascular medicine can advance and patient outcomes can be improved by addressing these gaps through interdisciplinary collaboration and technological innovation. This will pave the way for more precise, personalized and timely interventions in the early detection and management of cardiovascular diseases.

Supplemental material

Supplemental data for this article can be accessed at https://doi.org/10.1080/17435889.2024.2364581

Author contributions

J Wang: data gathering and organization; writing initial manuscript; H Zhang: writing and reviewing initial manuscript; W Wan: writing and reviewing initial manuscript; H Yang: data gathering and organization, writing and reviewing initial manuscript; J Zhao: conception and design of the study; review and finalization of the manuscript; supervision and guidance of the work and finalization of the manuscript. All the authors read the final manuscript and agree to publish this work.

Financial disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

The Authors declare that they have no competing interests financial or non-financial or any other interests that might be perceived to influence the results and/or discussion reported in this paper.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.