On June 4, 2024, we conducted a comprehensive search in the Web of Science Core Collection (WOSCC) database. WOSCC, recognized as a premier academic information database, is distinguished by its selection of high-impact journals, which makes it particularly suitable for bibliometric analysis compared to other databases (23). In this study, we included only English-language publications categorized as “article” or “review”. Given the limited number of publications in the relevant field prior to 2004, the time span was set from January 1, 2004, to June 4, 2024. The specific literature selection process is depicted in Figure 1 .

This study primarily utilized Microsoft Excel 2021, R software (version 4.4.0), VOSviewer (version 1.6.19.0), and CiteSpace (version 6.1) for visual analysis. The bibliometrix package in R software is specifically designed for bibliometric analysis (24). In this research, we utilized this package to create graphical representations of keyword counts, showcasing visual maps of hotspot development trends. VOSviewer utilizes probabilistic data standardization methods for visualizing data and constructing various network connections (25, 26). In this study, we used VOSviewer to analyze associations among countries, institutions, authors, references, and co-occurrence of keywords. CiteSpace, a robust exploration tool widely used in data visualization, employs standardized data aggregation and burst detection methods to track emerging research trends and future directions (27). In this manuscript, we employed CiteSpace to analyze centrality data of countries and institutions, overlapped journal co-citation networks, and conducted burst detection analysis of references and keywords, generating visualizations accordingly.

The data utilized in our study were obtained from publicly accessible databases containing published articles. As the study did not involve animal or human subjects, ethical approval from a committee was deemed unnecessary.

From January 1, 2004, to June 4, 2024, a total of 2,843 publications related to nanoparticles in gynecologic cancers were identified in the WOSCC database based on the search criteria. Among these, 2,661 articles (93.6%) were research articles and 182 articles (6.4%) were reviews. As shown in Figure 2 , the number of publications steadily increased from 2004 to 2020. Although there was a slight decrease after 2020, the overall trend over the past 20 years has been upward. Moreover, from 2021 to 2023, the annual number of publications remained around 290, indicating sustained attention to nanoparticles in the field of gynecologic cancers research. Furthermore, there has been a notable increase in citations, rising from 4 in 2004 to 13,090 in 2023. This increase in citations further underscores the significant scientific impact and relevance of findings from this research.

Over the past 20 years, research on nanoparticles in gynecologic cancers has been conducted in 76 countries and regions. Table 1 lists the top 10 countries/regions by publication count. China leads with 1,042 publications, followed by the United States (n = 624) and India (n = 399). Figure 3A depicts the global distribution of publications in this field, showing concentrations in North America, Europe, and Asia. The collaboration network visualization for countries/regions, as shown in Figure 3B , depicts total link strength (TLS), which reflects the intensity of collaboration or co-occurrence between nodes. The width of the connecting lines indicates the levels of international collaboration. According to Table 1 , the top three countries ranked by TLS are the United States, China, and India. Centrality, which assesses the importance of nodes within a network, exceeds 0.1, indicating pivotal nodes with significant influence (28). Notably, despite ranking second in publication count, the United States exhibits the highest TLS and centrality, underscoring its predominant influence in this field ( Table 1 ).

With regard to institutions, Figure 3C shows the institutions with 10 or more publications. The top publishing institutions include the Chinese Academy of Sciences (n=105), Shanghai Jiao Tong University (n=55), University of Texas MD Anderson Cancer Center (n=52) and Sichuan University (n=52) ( Table 1 ). Of significance, the Chinese Academy of Sciences not only leads in publication quantity but also demonstrates the highest TLS and centrality, highlighting its central role in this research landscape.

Over the past 20 years, 637 journals have published 2,843 articles on nanoparticles in gynecologic cancers. Among these, 15 journals have published 30 or more articles. Table 2 shows that the International Journal of Nanomedicine has the highest number of publications (n=97), followed by ACS Applied Materials & Interfaces (n=72) and Journal of Materials Chemistry B (n=53). The International Journal of Nanomedicine covers various aspects of nanotechnology applications in biomedicine, focusing on the potential clinical applications of nanoparticles in disease diagnosis, prevention, and treatment. In terms of impact factor, ACS Nano (n=32, IF=17.1) ranks highest among these journals. ACS Nano, as one of the top journals in the field of nanoscience, highlights research achievements in nanoscience and nanotechnology. The journal is interdisciplinary, spanning fields such as chemistry, physics, biology, and engineering.

Figure 4 presents a dual-map overlay visualization of academic journals, illustrating the relationships between journals. Citing journals are shown on the left side, and the cited journals are shown on the right side. Research published in journals focusing on chemistry/materials/physics and molecular/biology/genetics is frequently cited by journals focusing on physics/materials/chemistry and molecular/biology/immunology.

A total of 15,227 researchers have contributed articles in the field of nanoparticles in gynecologic cancers. Sood, A K has published the highest number of articles (n=30), followed by Lopez-Berestein G (n=22) and Steinmetz, NF (n=16). The collaboration network map among authors indicates close cooperation among them ( Figure 5A ). Co-cited authors are authors cited together in academic research, forming co-citation relationships (29). Figure 5B displays the network visualization map of co-cited authors. Siegel, RL ranks first in citation count (n=221), followed by Zhang, Y (n=213) and Gurunathan, S (n=191). Table 3 outlines the citation counts for the top 10 co-cited authors, totaling over 1,700 citations, highlighting their significant influence in the field of nanoparticles in gynecologic cancers. It is noteworthy that Gurunathan, S is among the top ten authors in the current field and is also one of the top ten co-cited authors. In recent years, this author has made significant contributions to the biomedical application of nanoparticles such as graphene and silver nanoparticles (30–32). Furthermore, the author has delved deeply into the biological functions of exosomes, particularly their potential as delivery vehicles in cancer therapy and as emerging nanoplatforms in biomedical applications (33).

Table 4 outlines the top 10 co-cited references. These articles generally fall into three main themes: (1) cancer statistics, (2) nanoparticles in cancer therapy, and (3) research on cancer treatment methods and mechanisms. The two most co-cited articles are both from the prestigious journal “CA: A Cancer Journal for Clinicians,” focusing on global cancer statistics. The third most co-cited paper, published in Nature Nanotechnology, details a repository of nano-carriers and molecules for selective tumor targeting, emphasizing challenges in cancer treatment (34).

Figure 6A displays the co-citation network of references with 20 or more citations, divided into 5 clusters. Cluster 1 (red) primarily discusses nanotechnology applications in cancer therapy. Cluster 2 (green) focuses on the mechanisms of nanoparticle action at the cellular level. Cluster 3 (blue) centers on tumor data statistics. Cluster 4 (yellow) emphasizes drug delivery systems. Cluster 5 (purple) addresses challenges in clinical applications of nanomedicine. Figure 6B depicts a density visualization of references co-cited 20 times or more, with colors closer to yellow indicating higher cited volumes. It is evident that cluster1 (red) and cluster3 (blue) contribute significantly to the cited volumes.

Table 5 illustrates the top 25 references with the strongest citation bursts, with blue lines indicating the timeline and red segments representing burst intervals. Notably, 12 articles have experienced recent bursts, potentially indicating future trends in the field of nanoparticles in gynecologic cancers. Five articles focus on cancer data statistics, while four provide comprehensive reviews of two prominent types of gynecologic malignancies—ovarian and cervical cancers. The remaining three articles concentrate on cutting-edge therapeutic approaches for these diseases.

In the field of nanoparticles research related to gynecologic malignancies, Table 6 present the frequency distribution of the most commonly occurring 10 keywords. Among the top 10 keywords, excluding those directly related to the search terms, current popular topics include drug delivery, cells, therapy, apoptosis, expression, and release. Figure 7A presents the keyword co-occurrence visualization map with keywords appearing 10 times or more, comprising 484 nodes and 25,920 links. The size of each node representing a keyword is directly proportional to its frequency of occurrence. The graph can be divided into four major clusters based on different colors. The red cluster represents common gynecologic malignancies and treatment modalities, the green cluster includes commonly used nanoparticles in gynecologic malignancies, the blue cluster focuses on drug delivery systems, and the yellow cluster primarily discusses clinical mechanisms of nanoparticle action at the cellular level. Figure 7B displays an overlay visualization where keywords closer to yellow indicate recent significant impact, suggesting heightened attention on “silver nanoparticles”, “green synthesis” and “antibacterial” in recent years.

In addition to current and past keywords, future potential hotspots and development trends are analyzed in Figure 7C . The first quadrant signifies crucial and well-developed issues, the second quadrant indicates well-developed but currently less significant topics, the third quadrant represents emerging or declining topics, and the fourth quadrant denotes important but less developed issues in the field. The first quadrant includes the keywords expression, doxorubicin, and chemotherapy, which signify advancements in nanotherapy offering new avenues for refining traditional chemotherapy methods. In the fourth quadrant, keywords such as gold nanoparticles, cytotoxicity, toxicity, nanoparticles, drug-delivery, and delivery underscore the application of nanoparticles in drug delivery, while emphasizing the critical need for further exploration in related cytotoxicity and toxicity assessment studies.

Table 7 illustrates the top 25 keywords with the strongest citation bursts. Keywords such as “antioxidant,” “cervical cancer,” “endometrial cancer,” “antibacterial,” “epithelial ovarian cancer,” “green synthesis,” “gold nanoparticles,” and “cisplatin resistance” have garnered significant attention in recent years and are likely to continue to attract interest. This highlights ongoing interests and signifies potential trends in the field of nanoparticles in gynecologic malignancies.

Publications are crucial indicators for assessing the academic vitality and developmental trends of research fields, providing an objective reflection of research dynamics in specific domains (35). Figure 2 shows there has been a significant increase in publications related to nanoparticles in gynecologic malignancies over the past two decades. Approximately 85.72% (n=2437) of these publications are concentrated in the last decade. Notably, while the United States ranks second in publication volume, accounting for only about 60% of China’s output, its centrality is more than twice that of China’s, indicating substantial influence in the field. This phenomenon can be attributed to factors such as the high burden of gynecologic malignancies in the United States and robust healthcare investments (36, 37). The United States is a global leader in the field of nanomedicine, accounting for 46% of the global market share in 2016 (38). In 2018, the National Institutes of Health (NIH) invested an estimated $445 million in nanomedicine research (39). This substantial financial investment has provided a solid foundation for the development of nanomedicines, particularly in the area of anticancer therapies. While nanotherapy may offer an efficient treatment option, the high research and production costs may restrict its widespread use in resource-limited countries. Developing countries could reduce production and supply costs for nanotherapy through supportive policies, such as tax incentives and patent protection adjustments. Furthermore, establishing international collaboration platforms to share key technologies and research outcomes can help lower research costs.

What’s more, the Chinese Academy of Sciences not only leads in terms of publication volume but also stands out as the institution with the greatest influence. Although it collaborates with institutions such as the Massachusetts Institute of Technology, University of California, Los Angeles, and Dana-Farber Cancer Institute, most collaborations remain within China, including Shanghai Jiao Tong University, Sichuan University, Fudan University, and Zhejiang University. Considering the serious health threat posed by gynecologic malignancies and the tremendous potential of nanoparticles in treating these cancers, strengthening international collaborations among institutions is imperative to advance research in this field.

A total of 637 academic journals have published research articles on nanoparticles in gynecologic malignancies, with the top 15 journals accounting for 23.29% of the publication output. The International Journal of Nanomedicine leads in publication volume; however, there remains a shortage of high-impact factor journals in this field. Sood, A K and Siegel, Rl are respectively the most prolific and most cited authors in this domain. Sood, A K’s research includes liposomal nanoparticles for delivering small interfering RNAs(siRNA) in cancer therapy and the application of RNA-targeted therapy in ovarian cancer treatment. Liposomal nanoparticles enhance stability and bioavailability, effectively delivering siRNA to tumor tissues for RNA-targeted therapy, which plays a crucial role in treating gynecologic malignancies (40, 41). And Siegel RL has made outstanding contributions to cancer statistics (42).

Table 5 lists the top 25 references with the strongest citation bursts. The three articles with the highest burst strengths are all from the prestigious journal CA: A Cancer Journal for Clinicians. The strongest burst is attributed to the publication by Sung H et al. on the 2020 global cancer statistics (43), followed by the research on the evolving management of epithelial ovarian cancer by Lheureux S et al. (44), and the relevant study on cancer data statistics from 2009 by Jemal A et al (45). Excluding literature solely focused on the current status of gynecologic tumors and considering both the strength and time of burst, two articles deserve particular attention. The first article, authored by Patra JK et al., comprehensively reviews the discovery and application of nanoparticles, emphasizing their crucial roles in cancer therapy and diagnosis. For instance, oleic acid-coated iron oxide nanoparticles can be employed for cancer diagnosis using near-infrared, while hyaluronic acid-coated iron oxide can be used for cancer treatment (46). The second article, authored by Barani M et al., focuses on nano-scale drug delivery systems in ovarian cancer treatment, providing robust scientific evidence for targeted therapy in ovarian cancer. The utilization of nanobiosensors to evaluate biomarkers has illuminated a novel path for guiding treatment in ovarian cancer patients (47).

Keywords condense the essence and core of a paper, representing the central themes and topics of research. Analyzing keyword frequency and burst detection can reflect research hotspots and future trends in a field. Based on keyword clustering, we elaborated on the following two main aspects in detail:

(1) Nanoparticles for drug delivery

Targeted drug delivery systems generally refer to the use of nanomedicine carriers, such as nanoparticles, administered via routes like vascular injection, to deliver drugs to specific sites of disease (48). Nanocarriers demonstrate potential in delivering various anticancer drugs and enhancing treatment efficacy (49), achieving active targeting from passive delivery, prolonging drug circulation in the body, and effectively eliminating cancer cells (50). Currently, common nanocarriers used for drug delivery in gynecologic malignancies include liposome nanoparticles, polymer nanoparticles, and inorganic nanoparticles. Ledezma-Gallegos et al. developed liposomal nanoparticles co-encapsulating cisplatin and mifepristone, demonstrating significant cytotoxic effects against cervical cancer cells, thereby enhancing chemotherapy efficacy (51). Wang et al. also found that liposomes loaded with miRNA-1284 and cisplatin enhance the treatment of cervical cancer (52). Li et al. improved the tumor microenvironment and enhanced the efficacy of drugs against gynecologic malignancies using cancer cell membrane-modified nanoparticles loaded with dexamethasone (53). Although research confirms that liposome nanoparticles can enhance the treatment of gynecologic cancers, either directly or indirectly, their effectiveness in encapsulating highly hydrophobic drugs, such as paclitaxel commonly used in ovarian cancer treatment, is limited. This limitation arises because the liposomal structure resembles that of biofilms, which complicates drug retention within the liposomes (54–56). Furthermore, Clinical translation still faces numerous challenges, such as low drug-loading capacity and high uptake rates in the liver and spleen, which may affect treatment safety (56, 57). Polymer nanoparticles exhibit characteristics such as water solubility, excellent stability, and biocompatibility. Researchers like Wang demonstrated the significance of folate-modified, pH-sensitive polymer nanoparticles co-delivering carboplatin and paclitaxel in both in vitro and in vivo models for treating cervical cancer (58). However, several unresolved challenges remain. First, the synthesis of polymer nanoparticles is complex and costly, potentially hindering large-scale clinical applications. Moreover, further investigation is required to ensure that polymer nanoparticles remain stable in vivo, evade immune recognition, and minimize potential toxicity (59, 60). Inorganic nanoparticles mainly include gold, silver, oxides, etc. Due to their magnetic, optoelectronic, antimicrobial, and plasmonic properties, they offer unique advantages in diagnostics, lymph node imaging, fluorescence tracking, etc (61, 62). For instance, silver nanoparticle-modified amine-functionalized mesoporous silica nanoparticles show significant potential in delivering doxorubicin for cervical cancer treatment (49). However, clinical application is limited due to inherent toxicity of some inorganic nanoparticles (63). Given the distinct advantages and drawbacks of different types of drug-delivery nanocarriers, the number of nano-drugs applied clinically for treating gynecologic malignancies remains limited. For example, Food and Drug Administration (FDA) approval of Doxil (liposomal doxorubicin) widely used for treating metastatic ovarian cancer represents a major breakthrough in the field. In summary, nanomedicine carriers for treating gynecologic cancers, including liposomes, polymers, and inorganic nanoparticles, hold immense potential and face significant challenges in enhancing drug delivery efficiency and treatment efficacy. Currently, their clinical application remains limited. Enhanced interdisciplinary collaboration and the accumulation of clinical data will help to more comprehensively evaluate the actual effectiveness of nanodrug carriers in treating gynecologic cancers.

(2) Nanoparticles in the research of gynecologic cancers

Through keyword clustering analysis, we found that magnetic, iron-oxide, silver, and gold nanoparticles are frequently mentioned in the context of gynecological cancers. Taking ovarian cancer, which has the highest mortality and poorest prognosis among gynecological malignancies, as an example, early-stage detection is challenging due to the absence of specific clinical symptoms and sensitive biomarkers. Traditional tissue biopsy is considered the gold standard for diagnosis, but it can lead to cancer cell dissemination into the peritoneum during early ovarian cancer tissue sampling (64, 65). Nanoparticles demonstrate promising performance in these aspects. For instance, Pan et al. developed a simple and cost-effective method using folate-modified fluorescent magnetic nanoparticles to capture and identify circulating tumor cells in ovarian cancer patients, aiding in metastasis diagnosis (66). Similarly, Liu et al. utilized folic acid conjugated magnetic iron oxide nanoparticles to bind to overexpressed folate receptor and thus stably attach to the surface of ovarian cancer cells, rendering the cells magnetic and thus enabling the possibility of early detection of metastatic ovarian cancer cells (67). In addition to the aforementioned nanoparticles, silver and gold nanoparticles also play crucial roles. These nanoparticles not only serve as popular keywords but also represent future research trends and hotspots (see Figure 7C , Table 7 ). In vitro experiments demonstrate that triangular silver nanoparticles significantly inhibit ovarian cancer cell proliferation and growth, suggesting their potential as a future therapeutic approach (68). Silver nanoparticles exert cytotoxic effects by activating the p53 gene, thereby suppressing cancer cell growth. Interactions between gemcitabine and silver nanoparticles exhibit cytotoxicity in ovarian cancer cells (69, 70). Curcumin-coated silver nanoparticles act as sensitizers for cisplatin chemotherapy, potentially reducing side effects and enhancing efficacy (70, 71). Gold nanoparticles, similar to silver nanoparticles, enhance sensitivity of ovarian cancer cells to cisplatin (72). Upon binding with cisplatin, gold nanoparticles not only augment cytotoxic effects against tumor cells but also mitigate toxicity towards normal cells (73). Apart from enhancing cisplatin’s functionality, gold nanoparticles arrest cancer cells in the radiosensitive cell cycle phase (G2/M), further sensitizing them to radiation therapy (74, 75).

Beyond ovarian cancer, superparamagnetic iron oxide nanoparticles demonstrate extensive potential in the treatment of other gynecological malignancies such as cervical, endometrial, and vulvar cancers. This novel magnetic resonance lymphography technique utilizes iron oxide nanoparticles, avoiding the use of radioactive isotopes, and enables detection by magnetic resonance imaging devices following lymphatic transport to lymph nodes. However, further clinical application and research are needed to fully develop this technology (76–78). Additionally, silver nanoparticles enhance camptothecin’s therapeutic efficacy against cervical cancer cells compared to monotherapy (79). L-histidine-terminated silver nanoparticles also show promise as a potential effective treatment for cervical cancer (80). Furthermore, silver nanoparticles bind with DNA for detection purposes in gynecological malignancies (81). Gold nanoparticles not only directly induce BAX gene expression to induce apoptosis in cervical cancer cells but also form complexes with antibodies as Au@SiO2 nanoparticles for potential therapeutic applications in cervical cancer (17, 82). Moreover, gold nanoparticles act as sensitizers in radiotherapy and ultrasound irradiation, exhibiting synergistic effects (83). Therefore, nanoparticles such as iron oxide, silver, and gold nanoparticles demonstrate multifaceted clinical applications in gynecological malignancies.

Overall, silver and gold nanoparticles show diverse clinical potential in the treatment of gynecologic malignancies. However, most studies remain confined to laboratory and in vitro research, with insufficient clinical trial data to fully support their safety and efficacy. Challenges to broader application include their in vivo stability, potential toxicity, and possible immune responses (84). Balancing their anticancer effects with potential side effects to facilitate safer and earlier clinical use remains a pressing issue.

Based on emerging keyword trends (see Table 7 ) and a hotspot analysis ( Figure 7C ), this study outlines three future trends in nanoparticles for gynecologic cancers as follows:

Several limitations exist in this study. Firstly, we exclusively relied on the WoSCC database for our search. While WoSCC is commonly used for bibliometric analysis, it may not encompass relevant literature from other databases, which could lead to the omission of some pertinent studies. Secondly, our study only considered English-language articles, potentially overlooking non-English publications and thereby potentially reducing credibility. Lastly, articles included in our study spanned from January 1, 2004, to June 4, 2024, and the WoSCC database is continuously updated, suggesting that recently published literature may be underestimated.