Research Progress and Application of Nanotechnology in the

Treatment of Atherosclerosis

Shenyu Zhao

China Medical University‑The Queen’s University of Belfast Joint College, China Medical University, Shenyang, Liaoning,

110122, China

Keywords: Nanomedicine, Atherosclerosis Treatment, Targeted Drug Delivery.

Abstract: Atherosclerosis has attracted much attention in the field of disease treatment around the world. Among them,

improving the accuracy and efficiency of treating atherosclerosis is a common focus of the global community

and a difficult problem that has been studied. With the rapid development of biotechnology today, the

emergence of nanotechnology has become one of the excellent choices in the clinical field of medicine. In

recent years, nanotechnology has been used to understand the characteristics of atherosclerosis better and

effectively treat inflammatory sites and plaques in response to the complex pathology of atherosclerosis. This

review collects experimental data and research results on the current cutting-edge and promising

nanotechnology in treating atherosclerotic diseases and summarizes the development and application of this

technology. The article focuses on the important components and properties of nanotechnology; discusses the

mode of action and effective application of new nanotechnology in the field of atherosclerosis; combines

biological factors for targeted treatment and achieves preventive monitoring through new technologies. The

article also highlights the progress in the development of various types of nanotechnology and how they can

help to treat atherosclerosis more efficiently and stably. Therefore, this review aims to demonstrate the

profound impact of this technology on the treatment of atherosclerotic diseases, research in the field of

vascular diseases, and even similar multifaceted clinical medicine in the future.

1 INTRODUCTION

In recent years, atherosclerosis (AS), as a chronic

inflammatory disease, has been the main health

burden of global society because of its complexity

persistence, and diverse instability AS can cause a

series of cardiovascular and cerebrovascular diseases,

such as peripheral and carotid artery diseases and

cardiovascular diseases. Furthermore, similar multi-

disease complications can lead to the accumulation of

thrombosis in the arteries, compressing the plaques

and further exacerbating the disease. Serious medical

events caused by AS cause 17.9 million deaths each

year (Pan, et al.,2024). At present, traditional

treatment methods that mainly use lipid-lowering and

antihypertensive drugs can only solve early and basic

problems and their treatment has limitations. Drug

treatment has problems such as inaccurate

administration routes and non-regression of plaques.

At the same time, due to the systemic side effects of

some drugs, they are clinically limited, and this

similar basic treatment method cannot fill the gap in

the transformation between the mechanism and the

clinic.

Nowadays, with the rapid development of medical

biotechnology, popular nanotechnology is considered

to be one of the most promising emerging disciplines

in the clinical treatment of AS. Nanotechnology is a

new technology that combines knowledge from

multiple interdisciplinary disciplines such as material

science and physical chemistry. This technology has

achieved many application achievements in

biomedicine, environmental science, and other fields.

In terms of biomaterials, the ultra-small size gives a

larger specific surface area and more reaction sites,

making it easier to penetrate biological barriers and

having good biocompatibility. Secondly, the

physicochemical properties of the material can be

adjusted through controllable composition and

structure, and it can be used as a carrier to carry

cytokines for optimized treatment (Cheng, et

al.,2023). In terms of technical properties,

nanotechnology has a strong ability to deliver drugs

in a targeted manner, effectively solving problems

Zhao, S.

Research Progress and Application of Nanotechnology in the Treatment of Atherosclerosis.

DOI: 10.5220/0014400400004933

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 1st International Conference on Biomedical Engineering and Food Science (BEFS 2025), pages 75-81

ISBN: 978-989-758-789-4

such as low water solubility of drugs and improving

the efficiency of drug action. In addition, this process

prolongs the circulation time of drug factors and

reduces toxic side effects (Li, et al.,2022).

Nanotechnology has achieved remarkable results in

clinical treatment of different diseases.

Nanotechnology has been gradually applied to the

clinical treatment of AS with experimentally proven

feasibility and has even made relatively good

progress. This research is large in scale and lacks a

detailed and systematic review to guide development.

This review will begin with the structural

characteristics of different nanomaterials and the

direction of their disease treatment. And more

importantly, thus, this review will introduce the

existing applications of nanotechnology in the

treatment of AS from various perspectives of

nanomedicine; the future development and

challenges of nanotechnology in the clinical

treatment of AS.

2 STRUCTURAL PROPERTIES

OF DIFFERENT

NANOMATERIALS AND

THEIR DIRECTION OF

DISEASE TREATMENT

Nanomaterials are a new class of materials with

particle structures defined in sizes from 1 to 100

nanometers. The properties of nanomaterials, such as

thermal conductivity and thermal stability, quantum

size effect and surface effect, and even molecular

loading delivery of biological drugs, make

nanomaterials bring many new opportunities for the

development of medical technology. Not only that,

many nanomaterials have structures and properties

that have great potential in the treatment of different

diseases, and some of them have been well used in

clinical treatment (Zhu, et al., 2023). Therefore, the

next article selects the core commonly used

nanomaterials in both the organic and inorganic

nanomaterials sections to provide a detailed

description of their important functional properties

and disease treatment modalities.

2.1 Organic Nanomaterials

Organic nanomaterials, mainly composed of carbon

skeletons and biomolecules, have good degradability

and biocompatibility, and are widely used in

nanotechnology for drug delivery and imaging

therapy.

2.1.1 Lipid-Based Nanomaterials

Lipid-based nanomaterials contain liposomes, lipid

nanoparticles (LNPs), and solid lipid nanoparticles

(SLNs). These representative materials are of interest

for their lipid bilayer structure and tiny lipid

cholesterol molecules. Among them, liposomes are

composed of phospholipid bilayers wrapped around

an aqueous core, while SLNs are composed of lipid

monolayers wrapped around a solid lipid core. The

two most important representative materials are

structurally different, but they can be effectively used

in targeted drug delivery systems because they can be

surface-modified for good prolongation of blood

circulation. Both are used in inhalation therapy for

chronic lung diseases because they are very stable

during aerosolisation. Meanwhile, SLNs can utilise a

solid lipid core to achieve slow and controlled drug

release. SLNs loaded with berberine show good

bioavailability and produce an enhanced response to

antidiabetic effects (Chenthamara, et al., 2019).

2.1.2 Polymer-Based Nanomaterials

Polymer-based nanomaterials are divided into

nanomaterials based on natural polymers and

nanomaterials based on synthetic polymers

(including biosynthetic polymers and chemically

synthesised polymers). Natural polymers are a

renewable resource, such as chitosan, which has good

biocompatibility and degradability, allowing the

formation of polymer composites that are suitable for

delivery vehicles. At the same time, its adsorption and

humectancy can be chemically modified to produce

derivatives with properties superior to those of

chitosan, becoming a non-viral carrier with non-

immunogenicity and a large specific surface area,

which can be used as a delivery vehicle for vaccines.

For example, Newcastle disease virus (NVD)

encapsulated in N-2-hydroxypropyl

trimethylammonium chloride chitosan nanoparticles

(NDV/La Sota-N-2-HACC-NPs), which are low in

toxicity and safety, and which can sustainably trigger

stronger immune responses, can produce effective

results in immunomodulation. In addition to this,

synthetic polymers such as polylactic acid-

hydroxyacetic acid copolymers (PLGA), which can

control the rate of degradation by the ratio of lactic

acid to hydroxyacetic acid. Drug delivery

encapsulated in PLGA nanoparticles or microspheres

can effectively grow the duration of action of

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

chemotherapeutic drugs at the tumor site and reduce

adverse effects.PLGA improves the pharmacokinetic

properties of drugs and has become an excellent

material for controlled drug release worldwide (Han,

et al., 2018).

2.2 Inorganic Nanomaterials

Inorganic nanomaterials are mainly composed of

non-carbon-based inorganic elements or compounds

with unique magnetic and catalytic activities, which

are widely used in microenvironmental modulation

and targeted therapy.

2.2.1 Noble Metal Nanomaterials

Noble metal nanomaterials have many representative

materials, such as gold nanoparticles (Au NPs) and

silver nanoparticles (Ag NPs). They have been

prepared in a well-established method with good

surface modification, strong biocompatibility, and

excellent antimicrobial properties. One of the more

rapid developments is Au NPs, which, given their

excellent light absorption, can generate localized

surface plasmon resonance at specific wavelengths

for use in photothermal therapy (PTT) to treat

bacterial infections. Meanwhile, Ag NPs used in

combination with PTT and hydrogel under near-

infrared light and heat will induce heating of the

hydrogel on the wound surface and denaturation of

the proteins in the bacterial cells, which will promote

the release of Ag NPs. Such nanoparticles with a large

surface area and small size are more likely to enter

into the cell and chemically bond, leading to the

complete death of the bacteria. Both have great

potential in the biomedical field and co-processing

with other biotechnologies has led to an effective

increase in therapeutic efficacy (Wang, et al., 2022).

2.2.2 Silica-Based Nanomaterials

Silicon dioxide-based nanomaterials have achieved

success in a variety of disease treatment areas.

Among them, mesoporous silica nanoparticles

(MSNs) are the best-known and have many

advantages. Firstly, with very high flexible structural

properties, they have a huge range of pore sizes and

specific surface area, with a strong drug-carrying

capacity. Secondly, their hydrophilic surfaces have a

large amount of Si-OH, making them more

susceptible to functionalized modifications of

internal and external porous surfaces, which

significantly improves bioavailability, and

biocompatibility and enables a precise drug delivery

process, making them excellent bases for the

construction of various nanocomposites. MSNs have

a large number of biomedical applications, such as

MSN therapy itself, where Si ions released during

bone disease treatment can activate bone-related gene

expression, thereby stimulating cartilage

differentiation and bone recovery. For example,

MSNs are combined with polytherapy, which means

that multiple treatment modalities, such as

photodynamic therapy and enzyme-like catalysis, are

integrated into MSNs as an emerging targeted

therapy, which can lead to more stable and effective

targeted therapeutic outcomes. For example, the

desired material is combined in MSNs, and

upconversion NPs/MSNs nanocomposites are

inorganic nanomaterials containing lanthanide ions

with high biological tissue penetration. This material

can produce effective synergistic thrombolytic and

anticoagulant therapy in thrombolytic therapy, which

successfully promotes the efficiency of energy

conversion through different activators and

sensitizers (Xu, et al., 2023).

3 MULTIFACETED

DEVELOPMENT AND

APPLICATION OF

NANOTECHNOLOGY IN THE

FIELD OF

ATHEROSCLEROSIS

The mature development and diversification of

nanomaterials have made nanotechnology treatments

more and more perfect, and gradually applied in the

clinical treatment of many different disease areas.

This technology has been well developed and applied

to the AS treatment process, from targeted delivery

systems, diagnostic imaging tests, anti-inflammatory

and anti-oxidant interventions, plaque stabilisation

and elimination, and clinical combination therapy.

Nanotechnology solves the problem of AS disease in

many ways and is one of the excellent technologies of

modern medicine to solve AS through biotechnology.

3.1 Diagnostic and Therapeutic

Imaging

AS can monitor the degree of lesioning of plaques by

imaging, thus assessing the level of risk of the

disease, and providing diagnostic information and

corresponding treatment. The different characteristic

Research Progress and Application of Nanotechnology in the Treatment of Atherosclerosis

molecules will serve as markers for determining that

AS is not in the same disease level stage, and

therefore can be combined with nanotechnology for

detection and regulation, as well as accurate

treatment.

3.1.1 Fe₃O₄@M Biomimetic Nanoparticles

for Accurate Monitoring of Symptoms

of Early AS

In the early stages of AS, the adhesion molecule

VCAM-1, which is expressed on the surface of

activated endothelial cells, becomes a targeted

biomolecule for monitoring abnormalities in

endothelial cell production because it promotes

leukocyte recruitment to endothelial cell interactions.

Leukocytes do this by binding to the glycoprotein

α4β1 integrin, which is highly expressed on

macrophage membranes, and both can specifically

recognise and link VCAM-1. Based on the above

principles, Huang et al. synthesised bionic

nanoparticles, a technique in which Fe₃O₄

nanoparticles are coated with macrophage

membranes (Fe₃O₄@M）containing a large amount

of α4β1, which can be used to monitor VCAM-1 on

endothelial cells. This molecule is observed and

magnetic resonance imaging (MRI) is performed to

further understand and monitor changes in early AS.

Huang et al. performed pre-experiments in which

Fe₃O₄@M (targeted nanoparticles) and Fe₃O₄@P

(control nanoparticles) were injected intravenously in

an early atherosclerosis rat model. It was found that

the MRI signal intensity of the aortic root was

significantly reduced in atherosclerotic rats injected

with Fe₃O₄@M and there was no change in the signal

in the control group. This experiment demonstrated

that the bionanoparticles Fe₃O₄@M have the ability

to target early lesions of AS plaques, as well as the

ability to accurately monitor and with inspection

(Zhang, et al., 2023). Nowadays, different

nanoparticles for different periods of marker

molecules can effectively regulate the different stages

of disease that AS is in, and effectively diagnose and

prevent the risk of the disease.

3.1.2 LFP/PCDPD Multifunctional

Nanoparticles Targeted to Detect and

Treat AS

To further image the detection of AS and target

therapy for this disease, the research group of Xu et

al. constructed a multifunctional nanoparticle

(LFP/PCDPD) with reactive oxygen species (ROS)

corresponding to drug release, lipid removal, and

lipid-specific AIE fluorescence imaging. This

nanoparticle, which releases LFP at the lesion to bind

to the lipid to emit green fluorescence, enables lipid-

specific imaging. At the same time, this nanoparticle

has good imaging ability to monitor the extent and

location of the lesion more accurately. More

importantly than monitoring, in vitro experiments by

this group demonstrated that LFP/PCDPD can target

damaged endothelial cells, effectively enrich at the

site of plaque sclerosis, inhibit plaque formation, and

reduce the degree of inflammation. In terms of

experimental assurances, this nanotechnology is low

in toxicity and generates a ROS response and

controlled drug release, more comprehensively

targeted to address the clinical aspects of AS disease

(Xu, et al., 2022).

3.2 Targeted Delivery of Cytokines

In the treatment of AS, the targeted delivery system

can precisely regulate the plaque microenvironment

and accurately act on the lesions, improving the

therapeutic effect and reducing the side effects.

Similarly, nanomedicine targeted delivery of

cytokines brings more possibilities for the clinical

treatment of AS, both in the middle and end stages of

treatment.

3.2.1 Novel Targeted and Efficient

MM/RAPNPs Mimetic Nanoparticles

Wang and his group developed a biomimetic

nanoparticle designed to target AS, but conventional

targeted delivery systems suffer from problems such

as susceptibility to clearance by the immune system.

Therefore, the group developed a bionic nanoparticle

called MM/RAPNPs, which is a rapamycin (RAP)-

loaded PLGA nanoparticles (RAPNPs) combined

with a macrophage membrane (MM) coating. The

structure of this nanoparticle not only contributes to a

slow and long-lasting release of the drug, but also

successfully preserves macrophage membrane

functional proteins. More importantly, it enhances the

uptake of activated endothelial cells in vivo and

inhibits the proliferation of macrophages and vascular

smooth muscle cells, thereby reducing plaque

inflammation. In vitro, MM/RAPNPs treatment

significantly inhibited the course of AS lesions,

reduced lipid deposition and necrotic area, and

maintained vascular integrity. This technology passed

the characterisation test and safety assessment of

nanoparticles, which are potentially excellent carriers

BEFS 2025 - International Conference on Biomedical Engineering and Food Science

and can effectively inhibit the progression of AS

plaque inflammation, providing a new strategy for a

targeted drug delivery system for AS (Wang, et al.,

2021).

3.3 Nucleic Acid Nanostructures that

Accurately Connect Gene

Pathways: miR-146a-SPIONs

Bai and his group prepared a polyethylene glycol

(PEG)-coated superparamagnetic iron oxide

nanoparticle core (SPION) with non-cationic nucleic

acid nanostructures miR-146a-SPIONs attached to

phosphorothioate (PS)-modified miR-146a

oligonucleotides. This approach advances a boost in

the efficiency of gene therapy for AS, in which miR-

146a inhibits the activation of signalling pathways

associated with vascular inflammation and the PS

modification protects it from degradation by

nuclease. Firstly, multiple in vivo injections of miR-

146a-SPIONs significantly reduced plaque area and

stabilised plaques by enhancing collagen content in

the plaques. Secondly, this nanotechnology inhibits

the development of AS at the genetic level by

regulating genes related to lipid metabolism, immune

response, and signalling pathways. Finally, in vitro

tests have shown this efficacy to be effective in

accessing macrophages and endothelial cells, leading

to a reduction in plaque inflammation without

inducing severe toxicity. This nanotechnology is safe

and effective, revealing excellent prospects for

nucleic acid nanomedicine in AS (Bai, et al., 2022).

3.4 Plaque Elimination and

Inflammation Prevention in the

later Stages of Treatment

In clinical practice, the above nanotechnology

treatment options have good efficacy for AS and can

even reverse the progression of the disease. However,

after treatment by these nanotechnologies, residual

plaque elimination and inflammation prevention

become existential pitfalls that still have the chance

to lead to the recurrence of acute AS, even life-

threatening. In recent years, nanotechnology has been

developed while observing the structural changes of

advanced AS plaques to find new target site

opportunities for further thorough treatment.

Inflammatory response and plaque elimination is one

of the important issues in the end stage of AS

treatment, and the CANTOS study has shown that

methotrexate (MTX) combined with lipid core

nanoparticles (LDE) in combination with paclitaxel

(PTX) not only reduces the risk of cardiovascular

disease due to chronic inflammation, but also, by

choosing different nanoparticles, such as hyaluronic

acid nanoparticles (HA- NPs), it could produce

plaque stabilisation and anti-inflammatory effects. It

was found that its bionic NP white vesicles can mimic

the distribution of leukocytes accumulating at the site

of vascular injury, inhibit the release of inflammatory

factors and shrink the necrotic core of plaques by

delivering drugs to the inflammatory site of plaques,

resolving the destabilising factors arising at the later

stages of AS, so that the whole course of treatment of

AS can achieve the optimal expected results (Ou, et

al., 2021).

4 CONCLUSION

In this review, the article mainly summarizes the

existing development and therapeutic applications of

different types of nanotechnology in the clinical

treatment of AS diseases. In the process of collating

data and literature, this paper ensures that the topic is

related to nanotechnology, nanomedicine, and

nanomaterials. This article not only observes the

treatment directions of different nanomaterials for

different diseases but also connects and analyzes

atherosclerosis, which is the main focus of this article,

to obtain valuable research results of existing

nanotechnology from all aspects. In fact,

nanotechnology has become one of the important

technologies in clinical medicine today. Due to its

good biocompatibility, small size, large specific area,

controllable and adjustable structure, excellent

targeted drug delivery, and relatively mature

development level, it can undoubtedly be applied to

various diseases. At the same time, this article also

found that nanotechnology research in the field of AS

treatment has made significant progress. Among

them, the precisely targeted delivery system improves

the ability to eliminate inflammation and plaques, the

multifunctional integrated diagnosis and treatment

design, the controllable structural changes of

nanomaterials, and the rate and dosage of drug

release. All of the above advantages reflect the

advanced development of modern nanomedicine,

which almost surpasses the inefficiency, toxicity, and

recurrence produced by the traditional treatment of

AS in clinical practice. Therefore, within the novel

biotechnology, nanotechnology offers reliable and

innovative strategies for the treatment of AS in the

clinical field and also has very excellent prospects.

Research Progress and Application of Nanotechnology in the Treatment of Atherosclerosis

Focusing first on the structural properties of

different nanomaterials and the various directions for

the treatment of diseases, the article presents

examples of materials that are mainly used in modern

nanotechnology, in two separate sections: organic

nanomaterials and inorganic nanomaterials.

Examples include lipid-based nanomaterials and

polymer-based nanomaterials in organic materials,

and noble metal nanomaterials and silica

nanomaterials in inorganic materials. All of these

nanoparticles are important representatives of

nanomaterials, which are widely used in the fields of

environmental regulation and targeted therapy in

nanomedicine. Of course, different nanomaterials

have unique advantages and are suitable for use in

different diseases, and these nanomaterials are used

in combination with modern biotechnology to address

complex clinical medical diseases in a multifaceted

way. More importantly, understanding the general

principles of these nanomaterials can help connect to

the atherosclerotic diseases that the article focuses on.

Therefore, the authors focus on the existing

applications of nanotechnology in the treatment of AS

from several main aspects. From the beginning of the

diagnostic and therapeutic aspects of imaging, we

introduce Fe₃O₄@M nanoparticles, which can

accurately monitor the symptoms of early AS, and

LFP/PCDPD multifunctional nanoparticles, which

can detect and treat AS, with a focus on the diagnosis

and treatment of AS from an imaging perspective.

Then to the critical therapeutic period of targeted drug

delivery, introducing novel targeted and highly

efficient MM/RAPNPs mimetic nanoparticles and

miR-146a-SPIONs nucleic acid nanostructures that

accurately link genes. Finally focusing on the

elimination of plaque and inflammation in the later

stages of treatment, there are also many optional

nanomedicine strategies to prevent disease

recurrence. Thus, the data and applications

demonstrate that nanotechnology can address AS

disease and make a significant contribution to

cardiovascular disease.

The author aims to summarize the importance of

nanotechnology to AS and the entire medical field.

The importance of "nano" can be seen from the fact

that it has penetrated every aspect of life, and

nanomedicine has led to the prosperity of

biotechnology. This technology has good prospects in

terms of materials and technology, but it also brings

difficulties and challenges. For example, the in vivo

metabolic pathways and potential organ

accumulation risks of nanomaterials have not been

clarified; differences in plaque composition and

endothelial barrier penetration at different levels of

AS disease will weaken the universality of

nanocarriers; even if nanomedicine can prevent AS,

residual inflammation The possibility of recurrence

still exists; the cost of large-scale production and the

integrity of integrated diagnosis and treatment need to

be further improved. Therefore, this field should

focus on the joint research of "materials science-

molecular biology-clinical diseases" and combine

advanced artificial intelligence to produce

personalized treatment plans for patients. Finally, the

author hopes that people all over the world will work

together to overcome these existing medical problems

so that nanomedicine will play an increasingly

revolutionary role in the treatment of cardiovascular

diseases. Therefore, biotechnology will bring

methods and results, progress and breakthroughs, and

a great future to many medical fields in the future.

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