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. 2026 Jul 2;21(1):314. doi: 10.1186/s11671-026-04775-4

Bibliometric analysis of research trends on nanotechnology applications in atherosclerosis

Xiaoshan Zhang 1, Bo Ji 2, Zheng Liu 2, Yudong Zhang 2, Guan Wang 2, Yanan Zhao 2, Yue Zhang 2,✉
PMCID: PMC13328608  PMID: 42393462

Abstract

Atherosclerosis (AS) is a leading global health issue with limited traditional diagnostic and therapeutic precision. Nanomedicine, utilizing nanomaterials’ unique properties, offers promising innovative solutions for atherosclerosis diagnosis and treatment. Studies focusing on nanotechnology and atherosclerosis were retrieved from the Web of Science Core Collection. Relevant articles were selected for inclusion in the study according to the inclusion criteria. Bibliometric analysis of the included publications was performed via VOSviewer, CiteSpace and Bibliometrix. A total of 2682 publications were included in this analysis. From 1999 to 2025, the global academic paper output exhibited a significant upward trend. China, Harvard University, and Scholar Mulder, Willem J M were the most productive country, institution, and author. The International Journal of Nanomedicine was the journal with the highest publication volume. The research on the application of nanotechnology in AS has evolved from investigating disease basic mechanisms to targeted drug delivery therapy and imaging technology, and now to the stage of multi-mechanism collaborative therapy. Future development trends focus on research into extracellular vesicles, biomimetic nanoparticles, and NOD-like receptor family pyrin domain containing 3‌ (NLRP3) inflammasome. ‌Relevant research may accelerate cross-integration and provide useful directions for the treatment of atherosclerotic diseases. This bibliometric analysis summarizes the current application status and research hotspots of nanotechnology in atherosclerosis and identifies future application trends. These findings provide valuable insights into the utilization and development directions of nanotechnology in atherosclerosis.

Supplementary Information

The online version contains supplementary material available at 10.1186/s11671-026-04775-4.

Keywords: Bibliometric analysis, Atherosclerosis, Nanomedicine, Nanotechnology, Extracellular vesicles, Biomimetic nanoparticles

Introduction

Atherosclerosis (AS) is a chronic inflammatory disease involving large and medium-sized arteries [1]. It is the main pathological basis of cardiovascular and cerebrovascular diseases as well as peripheral vascular diseases [2]. The occurrence of AS is closely related to lipid metabolism imbalance and an abnormal inflammatory response, involving pathological processes such as lipid deposition, the inflammatory response, fibrous cap formation, plaque rupture, and thrombosis [3–6]. These changes may lead to severe complications such as myocardial infarction, stroke, and limb necrosis [7, 8]. Atherosclerosis is one of the main causes of incidence and mortality worldwide. According to statistics from the Global Burden of Disease (GBD) study, approximately 20 million people die from atherosclerotic diseases globally each year, with cardiovascular disease accounting for approximately 32% of total deaths worldwide and stroke accounting for approximately 11.6% [9–11]. These trends suggest that the global impact of atherosclerosis is increasing and that the healthcare burden of managing this complex disease is substantial.

In recent years, significant progress has been made in the treatment of atherosclerosis. Modern medicine employs statins, antiplatelet drugs, and circulation improving medications to slow the progression of AS [12]. However, long-term use of these drugs still result in complications such as liver and kidney function damage, low bioavailability, and a high risk of bleeding [13]. Therefore, exploring new treatment strategies for atherosclerosis is highly important for reducing the risk of vascular events, enhancing the targeting, effectiveness, and safety of disease treatment.

Nanotechnology is a technique for studying the properties and applications of materials within the range of 1 nm to 100 nm. Nanomedicine, which refers to the application of nanotechnology in medicine, is revolutionizing the diagnosis and treatment of various diseases, by leveraging the unique structure, as well as physical and chemical characteristics of nanomaterials [14]. Nanomaterials have gained widespread recognition for their unique properties in the accurate diagnosis and effective treatment of atherosclerosis [15]. First, nanomaterials achieve the diagnosis of atherosclerosis through high-precision imaging and molecular targeting. For example, nanoprobes can accurately locate and describe the morphology of atherosclerotic plaques and achieve three-dimensional(3D) visualization of plaques in the carotid artery and aortic arch [16]. When intravenously injected into mice, gold nanoparticles accumulate at sites of vascular inflammation, allowing the detection of carotid AS and abdominal aortic aneurysms [17]. Additionally, nanodrug delivery systems encapsulate drugs within nanocarriers. Nanocarriers can be engineered with precise size and surface modifications to achieve targeted delivery, allowing selective accumulation at lesion sites and significantly reducing systemic side effects [18]. This approach enhances drug targeting, stability, and bioavailability [19–21]. In the treatment of AS, nanoparticles enable the targeted delivery of statins and other therapeutic agents directly to atherosclerotic plaques, thereby increasing drug efficacy while minimizing systemic exposure. Furthermore, these carriers can safely transport noncoding ribonucleic acids (RNAs) for gene editing within plaque cells, facilitating precise cellular reprogramming and enabling novel therapeutic strategies [22–24].

Bibliometric analysis can effectively deal with the huge amount of literature, objectively analyze the current research status, and predict future research hotspots [25]. It quantifies publication trends, characteristics, and interconnections, thereby reflecting the dynamic trajectory of scientific research.

‌ Currently, researchers have conducted multilevel explorations into the application of nanotechnology in atherosclerosis from perspectives such as technological development and molecular mechanism studies, with progressively deepening insights. However, the existing literature remains fragmented, lacking systematic summarization and integration. There has been no comprehensive analysis of the research landscape, and developmental trends in the field of nanotechnology for AS. This study employs CiteSpace, VOSviewer and Bibliometrix alongside statistical methods to summarize recent literature on the application of nanotechnology in atherosclerosis from temporal and spatial dimensions. The aim of this study is to investigate the hotspots and future trends of nanotechnology applications in atherosclerosis, and provide fresh insights to advance nanomedicine exploration.

Materials and methods

Data collection and retrieval strategy

The Web of Science Core Collection (WOSCC) has been used to retrieve and obtain relevant literature on nanomedicine for atherosclerosis since its establishment. All the articles were retrieved on the same day to avoid confusion from partial results due to rapid updates in subsequent publications. The database retrieval work for this study was completed on January 2, 2026. The search database covered sub-databases in WOSCC, including the Social Science Citation Index (SSCI) and the Science Citation Index- Expanded (SCI-E) databases. The retrieval date was from inception of the databases to December 31, 2025.

The search strategy utilized in this study was set as follows: TS= (“atherosclerosis” OR “‌arteriosclerosis‌” OR “atherogenesis”) AND (“nano*”). The search term “nano*” was used to identify all terms, starting with “nano”. For example, TS= (“nanomedicine” OR “nanotechnology” OR “nanomaterial” OR “nanoparticle” OR “nanocarrier” OR “nanomachine” OR “nanoprobe” OR “nanoplatform” OR “nanovaccine” OR “nanogel” OR “nanodelivery” OR “nanorobot” OR “nanoliposome” OR “nanocapsule” OR “nanotherapy” OR “nanocomposite” OR “nanoformulation” OR “nanostructure” OR “nanosystem”). The search included only English-language publications of “Article” and “Review” types, while editorials, letters, books, book chapters, conference abstracts, retractions, errata, agreements, preprints, and other nonresearch materials were excluded.

Using terms prefixed with “nano” in the search helps avoid missing relevant literature due to terminology variations, ensuring comprehensiveness. However, “nano*” is broad and may include studies unrelated to the research topic, necessitating an added data selection process.

Data selection

The included publications and cited references were exported as plain text for bibliometric analysis and visualization. Two authors independently screened all studies by title, abstract, and/or full text to exclude irrelevant articles. Disagreements were resolved by a third author.

A total of 3550 articles were retrieved. In the preliminary screening stage, 227 articles were excluded due to language limitations and incompatible article types. After paper check, 157 duplicate articles were removed. The titles and abstracts of the remaining 3166 articles were subsequently screened, and ultimately, 2682 articles that met the inclusion criteria were included (Fig. 1).

Fig. 1.

Fig. 1

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Flowchart of the literature screening process

Data extraction and analysis

Metadata encompassing authors, institutions, countries, journals, publication years, and citation counts was extracted from the finalized literature corpus for comprehensive assessment.

CiteSpace(version 6.3.R2) [26] was employed for national and institutional contributions, prominent authors, co-cited reference clusters, and keywords analysis. Parameters included a time slicing from 1999 JAN to 2025 DEC, a time interval of 1 year, g-index(k = 25), Top N = 50, Top N%=10%, link retaining factor (LRF = 3.0), maximum links per node (L/N = 10), look-back years (LBY = 5), and e = 1.0. Pruning was not included among the configured parameters. “Slice frequency” was used as the default counting method for threshold determination. Visual elements, such as node size and label display, were normalized based on frequency. The maximum label length was adjusted to 30–50 characters to ensure the complete display of cluster labels, and the log-likelihood ratio algorithm was used to generate descriptive cluster labels. All other settings remained at default. Each node represents a country, institution, author, or journal. The size of each point corresponds to its importance (such as the frequency of occurrence). The lines between nodes indicate the relationships between two nodes (such as co-occurrence and collaboration), and the strength of the connection reflects the overall level of collaboration in the entire network [27]. The clustering quality of the graphs generated by CiteSpace is validated by a modularity value (Q-value) exceeding 0.3 and a mean silhouette value (S-value) exceeding 0.7, indicating robust and meaningful clustering structures [28].

VOSviewer (version 1.6.18) [29] was utilized for generating co-occurrence networks for core authors, countries, research institutions, and keywords. The parameters included setting the “counting method” to “full counting” and setting the “normalization method” to “association strength”. All other settings remained at default. Each cluster was displayed in a different color. The color of nodes represented their belonging to specific clusters, with nodes of the same color indicating strong associations. The color map based on years illustrates the evolution trend, where purple signifies earlier entry into the field and yellow represents more recent emergence.

The Bibliometrix package in R (version 4.5.1) [30] was used for trend analysis of literature output, evaluation of author influence, and statistical analysis of journal distribution. Additionally, we also conducted a visual analysis of the annual publication and citation trends via Microsoft Excel 2021.

Results

Main information about the metadata

A total of 2682 documents were identified through analysis of WOSCC using the constructed query and covering the years 1999 to 2025. Research articles constituted the predominant category, accounting for 77% of the total (2077 docs), while review articles comprised 23% (605 docs). Published between 1999 and 2025, these articles originated from 716 journals and involved 12,287 authors. The papers had an average of 38.45 citations, with a total of 117,889 references. Table 1 presents a comprehensive summary of ‌the main characteristics of the metadata.

Table 1.

Main information about the metadata

Category Description Results
General Information Timespan 1999:2025
General Information Sources (Journals) 716
General Information Documents (Docs) 2682
General Information Document Average Age 6.95
Growth Metrics Annual Growth Rate (%) 25.33%*
References and Keywords References 117,889
References and Keywords Author’s Keywords (DE) 5162
References and Keywords Keywords plus 5253
Authorship Details Authors 12,287
Authorship Details Mean Co-Authors per Doc 7.72
Authorship Details International co-authorships % 25.76
Authorship Details Single Author Docs 39
Citation Information Total times cited Doc 103,136
Citation Information Average citations per Doc 38.45
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*From 1999 until 2025 (counting 26 years)

Trend in publications and citations

Although we have been retrieving data since the establishment of the database, the earliest relevant research began in 1999, marking the start of nanoparticle applications in atherosclerosis. From the perspective of annual publication volume, research on nanomedicine in atherosclerosis from 1999 to 2025 has shown an overall growth trend, roughly divided into three stages. The first stage was 1999–2005, during which growth was relatively slow, with only 21 papers published over 7 years. The second stage was 2006–2018, during which publication volume increased steadily, although slight fluctuations were observed in 2017 and 2019. The third stage was 2019–2025, during which publication output increased rapidly, indicating growing scholarly interest in nanomedicine and atherosclerosis (Fig. 2). The publication growth percentage over the past years was calculated using the following formula [31], where n is the number of years, which equals 26 in this case:

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Fig. 2.

Fig. 2

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Annual distribution of publications and citations from 1999 to 2025

Based on this calculation, the publication growth rate indicated that scientific output experienced an important growth rate of 25.33%, as illustrated in Table 1. When examining total citations, despite periodic fluctuations, the overall trajectory showed a clear upward trend. Notably, between 2005 and 2006, citations experienced explosive growth, surging at an annual rate of 377.27%. The peak was reached in 2015, when total citations hit an all-time high of 8224. Furthermore, the relationship between publications and citations was explored. The findings unveiled a statistically significant positive correlation (r = 0.456; p < 0.05).

Analysis of publications and citations by country and institution

From 1999 to 2025, a total of 82 countries/regions participated in research on nanotechnology applications for atherosclerosis. Among them, the United States and China demonstrated outstanding performance in terms of publication volume and citation frequency, significantly outperforming other countries. As shown in Table 2, China led with 1049 papers and 27,368 citations, showcasing its research leadership in this field. The United States ranked first with an H-index of 114, which reflected its significant academic influence in this discipline. With respect to the centrality of the collaboration network, the United States (0.23), India (0.21), and England (0.20) ranked among the top three. The United States established close cooperative relationships with 44 countries/regions, becoming the core hub of the global collaboration network. In contrast, although China held a dominant position in research output, its centrality was only 0.13, with collaborations limited to 38 countries/regions, reflecting room for improvement in the breadth of its international cooperation. Notably, 57.32% of countries/regions (47 in total) collaborated with only 1–2 partners, including typical examples such as Brazil, Turkey, Australia, and New Zealand (Fig. 3). This distribution pattern highlights a significant “core-periphery” structure in global research on nanomedicine applications for atherosclerosis while also emphasizing the importance of strengthening international scientific collaboration to advance the field.

Table 2.

The top 10 most productive countries in nanotechnology for AS research

Rank Country Counts Total Citations Average Citations H-index
1 China 1049 27,368 26.09 76
2 USA 747 51,770 69.30 114
3 Germany 155 8923 57.57 45
4 India 121 4786 39.55 34
5 South Korea 110 4639 42.17 35
6 Netherlands 105 7538 71.79 46
7 England 92 3659 39.77 34
8 Iran 88 2048 23.27 26
9 France 84 3066 36.5 32
10 Japan 82 3617 44.11 33
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Fig. 3.

Fig. 3

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National cooperation network map

As shown in Fig. 4, a total of 521 institutions worldwide participated in research on nanotechnology applications for atherosclerosis, with the highest proportion of contributions coming from the United States and China. Among these institutions, Harvard University, Harvard University Medical Affiliates, and the Chinese Academy of Sciences were the top three. Harvard University stood out with 122 science citation index(SCI) publications, 13,046 citation counts, and an H-index of 61, securing the leading position (Table 3). The University of California system exhibited the highest centrality (0.21), indicating close collaboration with 61 other institutions. On a broader scale, most institutions demonstrated centrality values fluctuating between 0.01 and 0.05, reflecting relatively limited interinstitutional collaboration.

Fig. 4.

Fig. 4

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Institutional cooperation network map

Table 3.

The top 10 most productive institutions in nanotechnology for AS research

Rank Institution Country Counts Total Citations H-index
1 Harvard University USA 122 13,046 61
2 Harvard University Medical Affiliates USA 119 12,884 60
3 Chinese Academy of Sciences China 108 3108 30
4 Harvard Medical School USA 97 10,345 54
5 Shanghai Jiao Tong University China 69 2106 23
6 Massachusetts General Hospital USA 64 9365 45
7 Icahn School of Medicine at Mount Sinai USA 63 5205 41
8 University of California System USA 57 3621 28
9 Brigham & Women’s Hospital USA 54 5963 36
10 Sichuan University China 47 988 15
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Analysis of author publication volume and co-citation

From 1999 to 2025, a total of 12,287 authors contributed to research on nanotechnology for atherosclerosis. As shown in Table 4, Willem J. M. Mulder stood out with the highest SCI publication count, totaling 50 papers, which accumulated 4614 citations. His innovative work includes the creation of advanced nanoscale tracer technologies, which enable noninvasive dynamic monitoring of cellular activities and drug delivery in vivo [32, 33]. Additionally, he has pioneered the design of multimodal nanoscale tracers based on high-density lipoprotein (HDL), which are specifically engineered for real-time tracking of myeloid cells in ischemic heart disease via 19 F magnetic resonance imaging (MRI) [34–36]. These contributions have established him as a pivotal figure with significant influence in the domain of nanomedicine and molecular imaging. Additionally, Professor Ralph Weissleder synthesized the applications of magnetic nanomaterials for targeted imaging and therapy across biomedical fields such as atherosclerosis, cancer, and diabetes [37]. This work garnered significant recognition, amassing 779 citations. Furthermore, the centrality of these authors’ publications was relatively low, indicating limited collaboration, with only 5 clusters having formed among them (Fig. 5A and B).

Table 4.

The top 10 most productive authors in nanotechnology for AS research

Rank Author Counts Total Citations Publication Year H-index
1 Mulder, Willem J M 50 4614 2008 37
2 Fayad, Zahi A 46 4433 2006 37
3 Wu, Wei 31 1141 2019 17
4 Weissleder, Ralph 30 6730 2006 29
5 Nahrendorf, Matthias 25 4951 2006 23
6 Wang, Guixue 23 1166 2019 17
7 Wickline, Samuel A 20 1678 2006 18
8 Zhong, Yuan 20 308 2022 12
9 Lanza, Gregory M 19 1613 2006 17
10 Zhang, Kun 17 214 2023 10
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Fig. 5.

Fig. 5

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(A-B) Author cooperation network map. (C) Co-citation author network map

The co-citation analysis of the authors revealed that the three authors with the highest co-citation counts were Libby P (774 citations), Wang Y (349 citations), and Moore KJ (323 citations) (Fig. 5C). These findings indicate that their research has garnered significant attention from domestic and international peers, underscoring their substantial contributions to the exploration and development of nanomedicine in AS. However, despite their high citation counts, the centrality scores of these three authors were relatively low, with values of 0.08, 0.02, and 0.02. In contrast, Ross R presented a markedly higher centrality score of 0.28, significantly surpassing that of the other authors. This suggests that Ross R may occupy a pivotal position within the research network or serve as a key node at a critical turning point in the field.

Analysis of influential and co-cited journals

Between 1999 and 2025, a total of 716 journals published literature on the application of nanotechnology in atherosclerosis. As shown in Table 5, the top three journals in terms of publication volume were the International Journal of Nanomedicine (75 articles), ACS Nano (52 articles), and the Journal of Controlled Release (52 articles). The top three co-cited journals were Circulation (1652 citations), Arteriosclerosis, Thrombosis, and Vascular Biology (1478 citations), and Circulation Research (1307 citations) (Table S1 and Fig. 6A). Notably, the New England Journal of Medicine had the highest impact factor (IF) of 78.5. These findings indicate that nanomedicine applications in atherosclerosis research have garnered significant attention from scholars and are prominent in prestigious international journals, reflecting the field’s high academic influence. Furthermore, the data suggest that researchers should prioritize these key journals when reviewing literature to stay abreast of the latest advancements and consider them for potential submissions.

Table 5.

The top 10 most productive journals in nanotechnology for AS research

Rank Journals Counts IF(2025) JCR Division
1 International Journal of Nanomedicine 75 6.5 Q1
2 ACS Nano 52 16.1 Q1
3 Journal of Controlled Release 52 11.5 Q1
4 Biomaterials 50 12.9 Q1
5 ACS Applied Materials & Interfaces 45 8.2 Q1
6 Nanomedicine: Nanotechnology, Biology and Medicine 45 4.6 Q2
7 Journal of Nanobiotechnology 42 12.6 Q1
8 Pharmaceutics 40 5.5 Q1
9 International Journal of Molecular Sciences 37 4.9 Q1
10 Theranostics 36 13.3 Q1
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Fig. 6.

Fig. 6

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(A) Publication journal co-citation network diagram. (B) Dual-map overlay of journals

The knowledge flow of nanomedicine in application research for atherosclerosis can be visualized through a journal overlay map (Fig. 6B). In this figure, the left side represented the primary journal clusters in the Web of Science that focused on nanomedicine applications in AS (knowledge frontier), whereas the right side denoted the main cited journal clusters (knowledge background). The most prominent connections were observed between Topic 4 on the left (encompassing molecular biology and immunology), which extensively referenced Topic 8 on the right (involving molecular biology and genetics), and Topic 4 on the right (related to materials science and chemistry). The highest Z-value for these connections reached 5.742. These studies spanned multiple disciplines, including molecular biology, immunology, materials science, chemistry, and pharmacy. This trend indicates that nanomedicine research in atherosclerosis is progressively expanding its scope, manifesting a development trajectory characterized by multidisciplinary integration and fusion.

Analysis of co-cited references

Through co-citation analysis and clustering, we can systematically map the knowledge base of nanomedicine in atherosclerosis and identify its core research themes. In research on nanotechnology applications for atherosclerosis, a total of 1499 relevant literature documents had been identified (Fig. 7A). As shown in Table S2, the paper titled “The changing landscape of atherosclerosis” authored by Libby P [38] and published in Nature in 2021 stood out as the most frequently cited reference (155 citations), thereby establishing itself as one of the most influential publications in this field. ‌This article highlights a growing trend of AS among younger populations. The prevalence of traditional risk factors such as low-density lipoprotein cholesterol, hypertension, and smoking was declining. Emerging risk factors such as hypertriglyceridemia, sleep disturbances, and physical inactivity were gaining prominence in their contribution to disease onset. This finding holds significant importance for the individualized prevention and treatment of this disease. Similarly, Gao et al. [39] reported the development of a biomimetic drug delivery system using macrophage membrane-coated reactive oxygen species (ROS)-responsive nanoparticles. This innovative approach enables precise targeted therapy for atherosclerotic plaques while achieving synergistic inhibition of inflammatory progression and reversal of plaque deterioration. These findings establish a novel paradigm for the precision treatment of chronic inflammatory vascular diseases.

Fig. 7.

Fig. 7

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(A) Co-citation reference network map. (B) Co-citation cluster map of reference. (C) The top 20 references with the strongest citation bursts

Nanomedicine research on atherosclerosis yielded 7 well-clustered modules (Q = 0.699, S = 0.869). As shown in Fig. 7B, the most noteworthy modules included “responsive nanoparticles”, “atherosclerosis progression”, “contrast agent”, “atherosclerotic plaque inflammation”, “targeted atherosclerosis therapy”, “cholesterol efflux”, and “vasomotor dysfunction”. Vasomotor dysfunction, characterized by impaired vascular tone regulation, and defective cholesterol efflux, involving impaired removal of cellular cholesterol, are fundamental pathological drivers that contribute to plaque formation. Concurrently, inflammation of atherosclerotic plaques destroys plaque stability and aggravates vascular damage. A nanoparticle-targeted drug delivery system provides an innovative strategy for the treatment of atherosclerosis.

Figure 7C illustrates the top 20 references with the strongest citation bursts, which began appearing as early as 2006. The two most highly cited articles with the highest burst scores in the literature were “The changing landscape of atherosclerosis” (burst score: 33.62) and “Atherosclerosis” (burst score: 27.70), both authored by Libby P. These seminal works represent milestone contributions to the field.

Analysis of keyword co-occurrence and hotspots

Through the co-occurrence analysis of keywords, we can quickly capture the current hotspots and future research directions in this discipline [40]. The top 5 most frequently used keywords were “atherosclerosis”, “nanoparticles”, “inflammation”, “drug delivery”, and “in vivo”, indicating significant attention in this field (Fig. 8A). As shown in Fig. 8B and D, keywords such as “molecular imaging”, “ultrasmall superparamagnetic particles”, “angiogenesis” and “in vivo” were the main topics during the early stage. “Atherosclerosis”, “drug delivery”, “smooth-muscle-cells”, “oxidative stress” and “nanomedicine” have become recent research hotspots. Another crucial sign of the study frontiers and hotspots throughout time was the strength of the keyword bursts. The study further analyzed the top 25 keywords with the strongest citation bursts from 1999 to 2025 (Fig. 8E). The earliest burst keywords were “contrast agent” (2003, strength = 13.78) and “magnetic resonance imaging” (2003, strength = 12.07). “Molecular imaging” showed the strongest citation burst(strength = 19.02), which emerged in 2006 and subsided by 2013. The shift in burst patterns of keywords reflects the evolving research focus of nanomedicine applications in atherosclerosis. The emergence of keyword bursts can be used to identify the frontiers and trends of research fields. “Biomimetic nanoparticles”, “nlrp3 inflammasome”, “extracellular vesicles”, “cardiovascular diseases” and “system” continue to be hot topics in 2025.

Fig. 8.

Fig. 8

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(A-B) Keyword co-occurrence network map. (C) Visualization and clustering network of keywords. (D) Timeline view of keyword clustering. (E) The top 25 keywords with the strongest citation bursts

Figure 8C shows all keywords grouped into 10 clusters. The top 5 clusters of keyword clustering were as follows: Cluster #0 primarily concerned molecular imaging, including keywords such as “magnetic resonance imaging”, “contrast agents”, and “iron oxide”. Cluster #1 was related to extracellular vesicles, including “macrophage polarization”, “foam cells”, and “efferocytosis”. Cluster #2 focused on oxidative stress, including “cardiovascular disease”, “endothelial cells”, and “reactive oxygen species”. Cluster #3 emphasized drug delivery, including keywords such as “macrophage membrane”, “targeted delivery”, and “molecular imaging”. Cluster #4 was associated with HDL cholesterol and included keywords such as “lipid metabolism” and “cholesterol efflux”.

Discussion

Analysis of current research status

This study presents a systematic bibliometric analysis of nanotechnology applications in atherosclerosis research spanning the period 1999–2025. The analysis encompasses contributions from 12,287 authors affiliated with 521 research institutions across 82 countries and regions. By delving into the current landscape of nanotechnology’s utilization in atherosclerosis research, we offer valuable insights to guide future research efforts.

From the perspective of publication status, this field of research was still in the early exploratory stage before 2005, with nanomedicine failing to gain traction among scholars in atherosclerosis research. It was not until 2006 that the number of papers focusing on nanotechnology applications in AS entered a steady upward trajectory. Post-2018 witnessed a dramatic surge in publication output, marking a period when nanomedicine gained widespread recognition and intense interest within the AS research community.

From a global perspective, research on nanomedicine for atherosclerosis has formed a collaborative, multi-country landscape with the United States and China at its epicenter. The leading status of these two nations has established a high-level research platform in the field, pioneering new avenues for global AS treatment. This phenomenon is largely attributed to robust scientific research investment, well-developed medical research systems, and interdisciplinary innovation ecosystems in China and the US. These elements form the cornerstone of nanomedicine’s advancement. However, cross-country and cross-institutional collaboration remains inadequate, and regions such as Africa and South America have shown limited engagement in this field. Thus, broader international cooperation is still needed to better address such medical challenges.

From the perspective of disciplines and journals, numerous Journal Citation Reports (JCR) Q1 journals, such as the International Journal of Nanomedicine and ACS Nano, focus on nanomedicine research, solidifying nanomedicine’s important position in atherosclerosis. They guide researchers to accurately identify authoritative literature sources and grasp cutting-edge research trends. Multidisciplinary integration is another defining feature of this field: molecular biology deciphers atherosclerosis pathogenesis, immunology explores inflammation regulation mechanisms, materials science engineers targeted drug carriers, and cross-disciplinary collaboration drives the depth advancement of nanomedicine for AS. This landscape has emerged not only because the complex pathological mechanisms of atherosclerosis demand collaborative efforts across disciplines to unravel, but also due to the inherent cross-border applicability of nanotechnology. In the future, interdisciplinary cooperation should be further strengthened, leveraging the academic influence of top journals to advance the research and translation of nanomedicine for atherosclerosis.

Analysis of knowledge foundation

Highly cited references and their clustering studies constitute an important knowledge base in this field. Through cluster analysis of highly cited literature on the application of nanotechnology in atherosclerosis, seven core knowledge areas were identified, roughly divided into three levels: the pathological mechanism of atherosclerosis, the application of nanomaterials, and targeted delivery and therapy.

The pathological mechanisms of atherosclerosis are related to lipid accumulation, inflammation of the arteries, vascular endothelial injury [41]. Plaque inflammation offers a molecular basis for nanoparticle targeting, as abnormally expressed inflammatory factors in lesions can mediate nanoparticles to trigger on-demand drug release. Vasomotor dysfunction exacerbates vascular endothelial damage, creating favorable conditions for the adhesion and colonization of nanoparticles at lesion sites [42]. Insufficient cholesterol efflux leads to lipid deposition, a driver of AS progression and a target regulated by nanocarrier-mediated therapeutic agents. A diverse array of nanocarrier systems, including lipid-based vectors, polymeric nanoparticles, and hybrid constructs such as metal-organic frameworks (MOFs), have been engineered to selectively target key pathological components of atherosclerotic plaques [43, 44]. Targeted atherosclerosis therapy relies on nanoparticles to enable precise delivery of therapeutic agents to AS lesions and avoid systemic toxicity and side effects [45]. Thus, by virtue of the targeted delivery and intelligent drug release properties of nanoparticles, nanomedicines exert precise effects on key pathological processes of atherosclerosis including plaque inflammation, cholesterol efflux disorders and vasomotor dysfunction, facilitating accurate intervention in atherosclerosis pathogenesis [46–48].

The formation of the research foundation is closely tied to the intricate pathological mechanisms of atherosclerosis. Nanomedicine, with its distinctive advantages, enables synergistic intervention across multiple targets and pathways. Based on this research foundation, as understanding of the disease’s molecular mechanisms deepens, researchers will delve deeper into these core areas. They will design nanomedicines and treatment strategies with greater precision to enhance the performance and therapeutic efficacy of nanotherapeutics. Meanwhile, strengthening cross-disciplinary integration will open up new research avenues, which holds profound guiding significance for advancing nanomedicine applications in atherosclerosis research.

Research trends, hotspots, and frontier directions

Keyword co-occurrence analysis reveals evolutionary shifts in nanotechnology research for atherosclerosis applications. From the keyword time zone map and keyword burst analysis, the application research of nanotechnology in the field of atherosclerosis can be divided into three stages. During the basic mechanism exploration period (1999–2006), keywords focused on the fundamental pathological processes of AS, such as atherosclerotic plaque, endothelial dysfunction, angiogenesis, inflammation, and low-density lipoprotein [49–51]. In this phase, researchers concentrated on investigating the complete pathological cascade of AS, ranging from initial vascular endothelial injury to lipid deposition, plaque formation, and plaque rupture. They elucidated the underlying mechanisms by which these processes damage vascular endothelial cells, promote inflammatory responses, and accelerate the progression of atherosclerotic plaques. During the period of targeted delivery and imaging technology (2007–2018), keywords centered on drug delivery, nanoparticles, superparamagnetic particles, and molecular imaging. Researchers developed a diverse array of nanocarriers including liposomes, polymer nanoparticles, and gold nanoparticles. By modifying surface ligands on these nanoparticles, they achieved precise drug delivery to lesion sites, reducing drug-induced damage to normal tissues and enhancing drug enrichment efficiency within plaques [52–54]. Concurrently, researchers leveraged materials such as superparamagnetic iron oxide nanoparticles and gold nanoparticles as imaging contrast agents, harnessing their unique physical properties to improve the resolution and sensitivity of imaging techniques like MRI and computed tomography (CT). These materials can enable precise localization and compositional analysis of plaques, and even facilitating the early detection of small, incipient plaques [55–57]. During the multi-mechanism synergistic therapy period (2019–2025), keywords centered on photodynamic therapy, photothermal therapy, extracellular vesicles, foam cells, and reactive oxygen species. Research has started to explore the combined application of multiple nanotherapies while investigating the intricate molecular mechanisms underlying disease progression. For instance, photodynamic therapy eliminates foam cells and neovascularization in plaques by generating reactive oxygen species, and photothermal therapy disrupts plaque structure via localized hyperthermia [58, 59]. Ultimately, precise modulation of the disease’s complex pathological processes is achieved through the combination of multiple interventions.

The research hotspots of nanotechnology in atherosclerosis applications focus on the pathological mechanisms of atherosclerosis, nanocarrier-based drug delivery, smooth muscle cell regulation, oxidative stress intervention, and the application of nanomedicine in disease treatment. The high incidence of atherosclerosis has driven researchers to continuously explore its pathological mechanisms and seek therapeutic targets. Breakthroughs in drug delivery technology have overcome the limitations of traditional drug therapies. The abnormal proliferation of smooth muscle cells and oxidative stress damage play key roles in AS progression. These mechanisms are the focus of intervention. The unique targeting and sustained-release advantages of nanotechnology meet the complex pathological needs of atherosclerosis, making it a hot topic in interdisciplinary research. Summarizing these research hotspots can help researchers quickly identify advanced or applicable research directions, avoid redundant studies, and hold important guiding significance for clinical practice.

The emerging trend of keywords indicate that research focus is shifting toward the targeting potential and drug delivery capacity of nanoparticles (including extracellular vesicles and biomimetic nanoparticles), the inflammatory regulatory mechanisms of the NLRP3 inflammasome, and the exploration of cutting-edge areas such as cardiovascular disease intervention. Extracellular vesicles are key mediators of intercellular communication and hold promise as novel biomarkers for the diagnosis and treatment of atherosclerosis [60]. With their biocompatibility and targeting capabilities, biomimetic nanoparticles are expected to enhance drug delivery efficiency and minimize side effects [61]. As a critical regulatory hub in inflammatory responses, research on the NLRP3 inflammasome deepens our understanding of the inflammatory mechanisms underlying atherosclerosis and lays the groundwork for developing anti-inflammatory therapies [62]. This research trend carries profound implications for future studies. Future research could investigate the specific mechanisms by which extracellular vesicles contribute to AS, and develop extracellular vesicle-based diagnostic and therapeutic techniques. Meanwhile, efforts should be intensified to advance the research and development of biomimetic nanoparticles, optimize their performance, and enhance the precision and efficacy of drug delivery. These research directions may promote the development of nanomedicine in the field of atherosclerosis and support future research for the prevention and treatment of cardiovascular diseases.

Challenges and future perspectives

Although nanomedicine has shown great potential in the treatment of atherosclerosis, the process of transitioning from experimental to clinical trials faces challenges, with the focus on three dimensions, including safety assessment, production and cost control, and clinical validation and regulatory approval.

Biosafety is critical for translating nanomedicine to the clinic [63]. While nanomaterials’ unique physicochemical properties enable superior targeting and penetration, they also carry risks. Some nanocarriers can trigger immune activation, inflammation, or apoptosis, with repeated use amplifying such adverse effects [64]. Metallic nanocarriers may accumulate long-term in organs like the liver and even cross the blood-brain barrier. Their long-term metabolism and toxicity remain unclear, demanding further research [65].

Process consistency stands as a major barrier to nanomedicine industrialization. While promising in labs, large-scale production faces bottlenecks in batch consistency, process stability and cost control, due to a lack of unified characterization methods and quality standards [66]. Nanoparticle synthesis is highly sensitive to environmental factors, requiring advanced facilities and high purity materials that drive up costs beyond what healthcare systems and patients can afford.

Clinical validation and regulation of nanomedicine are fraught with hurdles. A lack of unified definitions, classification systems, and regulatory standards, ‌combined with‌ post-scaling stability issues, ‌hinders‌ its advancement [67–70]. Global regulatory frameworks remain underdeveloped, with inconsistent classification as either medicine or medical device leading to divergent approval criteria across countries [71]. Meanwhile, conventional drug evaluation systems are ill-suited to nanomedicines’ unique properties, leaving them without a tailored approval pathway.

Future research could focus on three directions. First, developing intelligent nanosystems, combining artificial intelligence (AI) and machine learning algorithms, optimizing nanomaterial design, and achieving precise spatiotemporal regulation of drug release. Second, promoting global regulatory collaboration, standardizing the definition and classification of nanomaterials, formulating specialized regulatory guidelines, and engaging in multi-party collaboration to cut down enterprises’ developing costs. Third, breaking through large-scale production bottlenecks, advancing continuous flow synthesis, promoting microfluidic controlled preparation and other processes, and accelerating technological transformation.

Limitation

While this study offers a broad perspective and reference for trends, it has certain limitations. First, this study draws data from WOSCC, which is dominated by journals from European and American countries. It does not incorporate other databases such as Scopus or PubMed, potentially overlooking research contributions from other regions and emerging research directions not covered by Web of Science. Second, this study restricts itself to English-language literature to avoid issues like translation discrepancies and cross-lingual terminology inconsistencies. However, this approach may lead to the oversight of research from non-English sources, potentially missing out on the unique characteristics and contributions of studies from different regions. Third, variations in literature retrieval strategies and search terms may introduce irrelevant content or lead to the omission of relevant research, thereby making the research incomplete. Fourth, the algorithms underlying commonly used clustering analysis software (CiteSpace and VOSviewer) differ. Given their distinct clustering logics and parameter settings, these tools may yield divergent clustering results. In addition, citation-based indicators may be influenced by time-dependent citation bias, because older publications have had more time to accumulate citations than recently published studies. This may affect the comparability of impact metrics across different time periods within our selected span.

Conclusion

This study presents a systematic review of nanotechnology applications in atherosclerosis through bibliometric and visual analysis. Publications and citations in this field are on the rise, with China, the United States, and their academic institutions making significant research contributions. The research on the application of nanotechnology in atherosclerosis has evolved from investigating disease basic mechanisms to targeted drug delivery therapy and imaging technology, and now to the stage of multi-mechanism collaborative therapy. Future development trends focus on research into extracellular vesicles, biomimetic nanoparticles, and the NLRP3 inflammasome.

In summary, nanotechnology has shown growing influence on the diagnosis and treatment of atherosclerosis, boasting certain development potential. The findings of this article can help researchers grasp the current research status, development trajectory, and evolutionary trends in this field. The findings may provide data support for scientific research decision-making, academic research, and resource allocation.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1 (54.5KB, doc)

Acknowledgements

Not applicable.

Author contributions

Conceptualization: Xiaoshan Zhang and Yue Zhang; data collection, analysis and data standardization: Xiaoshan Zhang, Bo Ji, and Zheng Liu; original draft preparation: Yudong Zhang and Yanan Zhao; review and editing: Guan Wang and Bo Ji; visualization: Xiaoshan Zhang and Yue Zhang. All the authors contributed to the article and approved the submitted version.

Funding

This study was supported by the Shandong Provincial Natural Science Foundation (Grant No.ZR2025MS1256) and ‌the Shandong Province Traditional Chinese Medicine Science & Technology Project ‌(Q-2023039).

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent to publish

Not applicable.

Competing interests

The authors declare no competing interests.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

Supplementary Material 1 (54.5KB, doc)

Data Availability Statement

No datasets were generated or analysed during the current study.

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