We conducted a bibliometric analysis using publications retrieved from two major academic databases: the Web of Science Core Collection (WoSCC) and Scopus, selected for their extensive coverage of peer-reviewed literature. The search was restricted to English-language articles and reviews published between 2001 and 2025. The final retrieval was performed on July 1, 2025, ensuring a consistent cutoff for all included records. The full search strategy is provided in Supplementary Material (Supplementary Table S1). Initial retrieval yielded 961 records from WoSCC and 949 from Scopus.

To address overlap between databases, duplicate records were identified and removed using the R -bibliometrix package (v4.3.0), which matches entries based on title, author list, publication year, and DOI (12). After deduplication and application of eligibility criteria (i.e., inclusion of only original research articles and review papers), the final dataset was used for all subsequent analyses.

A multi-method bibliometric approach was employed. Co-occurrence networks of keywords, authors, institutions, and countries were constructed using CiteSpace (v6.2.R3) to visualize collaboration patterns and thematic structures. Publications were divided into four time slices (2001–2007, 2008–2013, 2014–2019, 2020–2025) for cluster analysis based on the Log-Likelihood Ratio (LLR) algorithm. Kleinberg’s burst detection algorithm identified emerging topics, while betweenness centrality highlighted pivotal nodes in the networks.

Intellectual development was traced through reference-based clustering and citation timeline graphs, supplemented by burstiness maps for keywords and references. HistCite Pro (v2.1) was used to compute Local and Global Citation Scores (LCS/GCS) to identify seminal works. An Alluvial Flow Diagram was generated from CiteSpace keyword co-occurrence data to illustrate thematic evolution. Trend analysis was performed in R, with donut charts depicting the temporal distribution of research categories (Figure 1). All raw data were preprocessed in Microsoft Excel (WPS 2021) for cleaning and descriptive summarization prior to specialized bibliometric analysis.

After deduplication, 1,316 publications were identified from WOSCC and Scopus combined (961 from WOSCC, 949 from Scopus, 594 overlapping) (Figure 10A; Supplementary Table S2). Annual output was <10 before 2005, rose steadily after 2010, and exceeded 100 in 2024 (Figure 10B). Nonlinear regression showed exponential growth (combined R² = 0.9729) (Figure 10C). China led in output (659), followed by India (123) and the U.S. (103); Iran (44), South Korea (38), Italy (31), and Egypt (27) also ranked highly (Figure 10D). Institutionally, Egyptian Knowledge Bank (93), Xi’an Jiaotong University (88), and other Chinese institutions dominated the top ten (Figure 10E).

To assess the reliability and consistency of bibliographic databases in mapping academic collaboration networks, collaboration networks at the author, country, and institution levels were constructed using WOSCC and Scopus. Co-occurrence relationships of high-output authors, countries, and institutions were visualized using VOSviewer, validating the stability and complementarity of the two databases in revealing collaborative network structures.

In the author collaboration network, both databases identify several tightly connected sub-communities, indicating core research teams in the field. Chinese author groups (e.g., “Zhang,” “Chen,” “Li”) appear in both networks, reflecting a strong domestic collaboration network. However, international scholars such as “Smith” and “Johnson” exhibit different connection strengths and placements across the two databases. Scopus displays a more dispersed international network, while WOSCC emphasizes domestic cooperation. This disparity may stem from differences in journal coverage, language preferences, and citation standards (Figure 11A). While both databases align in identifying major collaboration groups, slight discrepancies in localized collaborations suggest the value of combining data from multiple sources.

At the country level (Figure 11B), both WOSCC and Scopus place China at the center, reflecting its dominant role in global collaborations. WOSCC shows a “central-radiation” structure, with strong ties to the U.S., India, and Iran. Scopus, however, features a more complex network, emphasizing connections not only with Western countries but also with emerging nations in the Middle East and Africa, particularly Egypt and Saudi Arabia. The United States appears more centrally in Scopus, while its connections in WOSCC are less pronounced, likely due to Scopus’s broader inclusivity of non-English journals and regional publications.

At the institutional level (Figure 11C), WOSCC highlights a tightly interconnected network of Chinese institutions, with Xi’an Jiaotong University at the center. In contrast, Scopus presents a more flattened network, focusing on multinational collaborations, such as those involving the Chinese Academy of Sciences and the University of Georgia. Scopus also highlights the Egyptian Knowledge Bank, a connection not as strongly represented in WOSCC, suggesting that Scopus is better at capturing the collaborative involvement of regional knowledge platforms.

While both databases align in identifying key research hubs (e.g., China, Xi’an Jiaotong University, Zhang), they differ in their emphasis on international collaboration and the diversity of collaborative patterns. Scopus captures a broader international scope, especially among developing countries, while WOSCC focuses on stable collaborations among traditional research powerhouses. Despite these differences, the core collaboration patterns remain consistent, and the parallel analysis of both databases enhances the reliability and comprehensiveness of the results, offering a more complete understanding of global research collaboration dynamics.

Our bibliometric analysis reveals a notable advancement in research on nanotherapy for UC, particularly between 2001 and 2025, with a significant increase in the number of publications. From 2001 to 2013, the volume of literature remained relatively modest. However, starting in 2014, the number of studies increased sharply, particularly in recent years, marking a phase of rapid development in this field. This research demonstrates the highly collaborative nature of the discipline, with strong networks of authors, institutions, countries, and research teams providing substantial support for its further advancement. Notably, countries such as China, the United States, India, and South Korea, along with prominent research institutions such as the Chinese Academy of Sciences and the University System of Georgia, have played a pivotal role in fostering global cooperation within this area.

In terms of research hotspots, changes in keywords over the past 16 years reflect the interdisciplinary nature of nanotherapy in UC treatment. For instance, “gut microbiota” has shown a significant surge between 2023 and 2025, underscoring the growing importance of the gut microbiome in UC therapy. Additionally, the emergence of terms such as “immune modulation” and “polymeric nanoparticles” highlights the integration of immune system regulation and drug delivery technologies in the development of novel nanomaterials. Furthermore, strategies for targeted delivery in UC, such as colon-specific drug delivery and the restoration of intestinal barrier function, have become focal points of research, illustrating the potential of nanotechnology in precise disease treatment.

By analyzing keyword flow diagrams and citation networks, we observe a shift in the application of nanoparticles in UC treatment from basic research to clinical translation. Throughout this process, drug delivery systems, intestinal targeting therapies, and the precise modulation of the inflammatory microenvironment have emerged as key topics.

UC is a prototypical chronic inflammatory bowel disease, characterized by prolonged inflammation that not only damages intestinal tissues but also compromises intestinal barrier function and induces immune system abnormalities (13). Traditional therapies often face limitations in efficacy and significant side effects. However, nanotherapy, with its excellent targeting capabilities, controlled release mechanisms, and multifaceted modes of action, presents promising therapeutic potential (14). As nanotechnology advances, nanoparticles, as drug carriers, not only enhance drug bioavailability and release profiles but also modulate inflammation, repair the intestinal barrier, and regulate the immune microenvironment, offering innovative solutions for UC treatment. This section summarizes key mechanisms of nanotherapy in UC treatment, detailing how they interact with the pathophysiological features of UC to provide more efficient and precise therapeutic strategies.

Nanotherapy is emerging as a promising approach for ulcerative colitis (UC), offering targeted drug delivery, biocompatibility, and tunable design—advantages over traditional therapies hampered by limited efficacy and side effects. With growing translation from preclinical studies to clinical trials, its clinical potential is increasingly evident.

Although aminosalicylates, corticosteroids, immunosuppressants, and biologics have long been the cornerstone therapies for ulcerative colitis (UC), these conventional treatments exhibit certain limitations regarding efficacy, systemic side effects, and patient adherence (45). For instance, corticosteroids, while effective in suppressing inflammation, may lead to metabolic disturbances and an increased risk of infections with prolonged use. Immunosuppressants and biologics, though highly efficacious, demonstrate variable responses due to patient disease phenotype heterogeneity and may induce systemic immune suppression (46).

In contrast, nanotherapy has shown considerable advantages in the treatment of UC. By enabling targeted delivery to inflamed colonic regions, nanoparticles can enhance the local drug concentration while minimizing systemic exposure, thereby reducing the risk of toxicity (47). Moreover, multifunctional nanoplatforms can simultaneously regulate multiple pathogenic pathways, including immune dysregulation, oxidative stress, and intestinal barrier damage, which are often beyond the scope of single conventional drugs (48).

Compared to emerging therapies such as gut microbiota transplantation or small-molecule inhibitors, nanotherapy offers greater flexibility in drug design, controlled release, and multifunctional integration. Therefore, nanotherapy holds promise as a powerful complement or alternative to traditional drugs and emerging therapies, addressing the multifaceted limitations of current treatments.

Nanotherapeutic approaches have demonstrated early momentum toward clinical translation in ulcerative colitis (UC). Available evidence, primarily derived from early-phase and exploratory studies, indicates that orally administered nanoformulations may enhance local bioavailability, improve colon-specific drug delivery, and maintain acceptable safety profiles. Nonetheless, current support for clinical application remains limited, as most findings originate from preliminary investigations rather than large-scale, confirmatory clinical trials.

Several barriers continue to impede further translation. These include difficulties in achieving controllable and reproducible large-scale manufacturing, insufficient long-term assessment of biocompatibility and safety, incomplete clarification of regulatory approval pathways, and challenges in aligning nanotherapeutic strategies with existing treatment algorithms and precision medicine frameworks.

Progress in this field will therefore require coordinated multidisciplinary efforts, supported by rigorous preclinical validation and the establishment of standardized, reproducible evaluation criteria and translational frameworks. Future studies, conducted under stringent safety and efficacy assessment, may investigate the integration of nanodelivery systems with patient-specific disease characteristics, including gut microbiota composition, inflammatory biomarkers, and immune phenotypes, to improve therapeutic precision and controllability. In parallel, multifunctional nanoplatforms that integrate drug delivery with modulation of inflammatory or immune pathways may provide complementary therapeutic options for UC; however, their clinical relevance must be established through systematic, well-designed clinical investigations.

This study is subject to methodological limitations inherent to bibliometric analyses. First, data were drawn exclusively from the Web of Science Core Collection and Scopus and truncated on July 1, 2025, excluding publications from July to December 2025, which may underrepresent the most recent advances in rapidly evolving areas such as gut microbiota modulation and exosome-based nanotherapies. Moreover, the reliance on only these two databases may omit relevant studies indexed in other major sources such as PubMed or Embase, potentially narrowing the scope of coverage. Second, both databases predominantly index English-language, peer-reviewed journal articles, introducing potential language and source biases. This limitation may exclude valuable contributions published in non-English journals, conference proceedings, preprints, grey literature, or regionally focused research that does not conform to mainstream publication channels. Third, all thematic and structural insights were derived from algorithmic metrics, including co-citation, keyword co-occurrence, and burst detection, which reflect quantitative visibility rather than scientific quality, clinical relevance, or methodological rigor. Bibliometric approaches, by design, cannot assess the validity, reproducibility, or translational potential of individual studies. Fourth, keyword standardization and indexing rely heavily on automated database tagging, which may introduce semantic inconsistencies or fail to capture nuanced conceptual variations across disciplines. Additionally, author and institutional disambiguation was performed automatically, which may conflate distinct researchers or misattribute affiliations, particularly within large collaborative networks.

Despite these constraints, the dual-database approach enhances coverage and cross-validation, and the convergence of findings across multiple analytical dimensions strengthens the robustness of the results. To address these limitations in future work, we recommend complementing bibliometric mapping with qualitative systematic reviews or mixed-methods approaches that integrate expert appraisal of methodological quality and contextual interpretation of emerging trends. Overall, the resulting map of global research activity in nano-based UC therapies provides a transparent, data-driven foundation to inform future strategic planning and foster interdisciplinary collaboration.