Exploring the global landscape of aptamer-based cancer research: Insights from keyword analysis, emerging themes, and research hotspots

1. INTRODUCTION

Aptamers are short, single-stranded DNA or RNA oligonucleotides that can adopt highly specific three-dimensional conformations, allowing them to bind with high affinity and selectivity to a diverse array of targets, including small molecules, proteins, and entire cells [1]. Synthetic nucleic acid ligands are commonly termed “chemical antibodies” because of their analogous molecular recognition capabilities; however, they present several significant advantages compared to protein-based antibodies [1,2]. Aptamers are nonimmunogenic, chemically produced, highly modifiable, and stable across many physiological settings [3]. Their diminutive size facilitates more efficient diffusion into tissues and malignancies, augmenting their utility in targeted therapeutics and diagnostic imaging. Unlike antibodies, aptamers can be rapidly generated without the need for animals or immune system activation, making them highly reproducible and cost-effective. Their structural flexibility and chemical diversity have prompted significant investigation into their possibilities in cancer research, where specificity and precision are required [3]. The development of aptamers is predominantly facilitated by the Systematic Evolution of Ligands by Exponential enrichment (SELEX) process. SELEX involves repeated phases of binding, selection, and amplification to identify oligonucleotides exhibiting high affinity for a certain target [4].

The SELEX process has experienced significant advancements, particularly the development of cell-SELEX, which allows the direct selection of aptamers against whole cancer cells without requiring prior knowledge of specific biomarkers [5]. These technological improvements have enhanced the ability to identify aptamers that target tumor-specific antigens, cancer-associated receptors, and secreted exosomes. These advancements offered new opportunities in both fundamental and translational cancer research [6]. Aptamers have emerged as useful tools in cancer research, with significant implications across diagnostic, therapeutic, drug delivery, and molecular imaging fields. In diagnostic applications, these nucleic acid-based ligands serve as biorecognition elements within biosensor systems (aptasensors) and microfluidic lab-on-a-chip platforms, which allow the detection of tumor biomarkers, circulating tumor cells (CTCs), and cancer-derived exosomes [7,8]. Aptamers’ excellent sensitivity and specificity, often comparable to or greater than conventional antibodies, coupled with compatibility with electrochemical, optical, and microfluidic technologies, facilitate point-of-care diagnostics and real-time disease monitoring [9].

In cancer therapy, aptamers can function as direct blockers of oncogenic proteins or as precise carriers that deliver drugs, siRNAs, or nanoparticles to tumors [10,11]. Aptamer-drug conjugates have demonstrated strong efficacy in preclinical models, achieving enhanced tumor specificity with minimized systemic toxicity through in situ drug release [12,13]. In addition, aptamer-functionalized nanocarriers such as liposomes, graphene oxide (GO) particles, and exosome-mimetic systems, have been constructed to enable dual-action delivery of chemotherapeutic agents and diagnostic payloads [14–16].

Furthermore, in molecular imaging, aptamers conjugated with fluorescent markers, radioactive isotopes, or contrast agents enable high-resolution visualization of tumors via positron emission tomography (PET), magnetic resonance imaging (MRI), and optical imaging systems [17–19]. These advancements highlight the potential of aptamers to contribute to precision cancer therapy, nanomedicine, and advanced diagnostics, making them as promising candidates for future cancer management tools, although most applications remain at the preclinical stage [20]. Despite growing interest, several well-documented challenges slow clinical translation of aptamer platforms. Unmodified aptamers are prone to nuclease degradation and rapid kidney clearance, yielding short half-lives; chemical modifications and carrier systems help but rarely solve this fully [21]. After cellular uptake, many constructs are sequestered in endosomes, limiting target engagement [22]. Specificity can be context dependent, with off-target interactions and protein-corona effects. PEGylation can extend exposure yet may be undermined by anti-PEG antibodies [23]. Clinically, experience remains limited, for example, the nucleolin-targeting AS1411 showed minimal activity in a Phase II setting [24]. These constraints are driving work on nuclease-resistant chemistries, long-circulating and self-assembled carriers, and designs that promote endosomal escape.

Bibliometrics is the quantitative assessment of scholarly publications, using statistical methods to measure research output, impact, and trends in a field [25–28]. This method analyzes measurable features of the academic literature, such as publication and citation counts, authorship patterns, and keyword frequencies to discover a domain’s structure, growth, and dynamics. Common bibliometric tools include co-authorship networks, citation mapping, and keyword co-occurrence analyses [29]. These methods identify influential researchers, main journals, collaborative networks, research hotspots, and emerging topics. Bibliometric analysis can transform massive publication data into clear visualizations and trend maps that reflect a field’s academic evolution over time. In contrast to traditional narrative reviews, which often reflect interpretive subjectivity, bibliometric studies offer systematic and objective views that can be systematically reproduced [30].

In biomedical research, bibliometrics can serve as a valuable instrumental methodology. These studies offer systematic visualization of the novelty of ecosystems, monitor the distribution and impact of emerging technologies, and identify resource allocation and strategic decision-making. For example, bibliometric studies have recorded global research trends in cancer, nanotechnology, artificial intelligence in healthcare, and vaccine development. These analyses generate practical, evidence-based insights for stakeholders, including policymakers, academic institutions, and funding agencies, by mapping thematic priorities, identifying collaboration networks, and identifying the translational direction of scientific progress [31,32]. In emerging domains such as aptamer-based diagnostics and targeted cancer therapies, bibliometric tools offer a comprehensive perspective on the multidimensional character of these fields, indicating how diverse research strands meet and develop over time [33]. In addition, bibliometric methods are also valuable for highlighting under-researched areas, disparities in regional contributions, and patterns of international collaboration, thereby highlighting opportunities for encouragement of new interdisciplinary and cross-border partnerships.

Therefore, the current study aims to perform both bibliometric and thematic analytical approaches to provide a comprehensive bibliometric analysis of global research on aptamers in cancer. Specifically, the bibliometric component evaluates publishing output over the past two decades, identifying leading authors, countries, international collaboration networks, and other bibliometric indices. Simultaneously, the thematic analysis, based on author keyword clusters, qualitatively interprets thematically significant studies to contextualize emerging research themes and translational progress. Together, these complementary methodologies yield a quantitative mapping and a qualitative synthesis of the aptamer–cancer research landscape, establishing a solid foundation to lead future studies and inform strategic initiatives in biomedical innovation.

2. METHODS

3. RESULTS

3.1. Annual publication output

A total of 2,721 articles were retrieved for analysis. Over the period from 2005 to 2024, the annual publication output on aptamers in cancer showed a steady upward trend, with an approximate average annual growth of 21.0%. This sustained increase mirrors the typical developmental trajectory of emerging research fields. In particular, the field experienced pronounced surges of activity in certain years, indicating peak research interest during those periods. The bulk, including 1,425 documents or 52.4 %, were published from 2019 to 2024. Figure 1 illustrates an integrated graph depicting the yearly volume of research articles generated alongside their associated citation trends.

Figure 1. Annual publication and citation trends in aptamer-based cancer research (2005–2024). The bar chart represents the yearly number of publications, while the line plot illustrates cumulative citations over the same period. Data were retrieved from the Scopus database. The x-axis denotes publication year, and the dual y-axes indicate publication count (left) and total citations (right). This figure illustrates the steady increase in research activity and impact across two decades. [Click here to view]

3.2. Leading journals

3.6. Bibliometric mapping

3.6.1. International collaboration

The global collaboration landscape in aptamer-based cancer research demonstrates a highly interconnected and dynamic network, as visualized through VOSviewer mapping (Fig. 2). In these visualizations, countries are depicted as nodes, with the size of each node corresponding to either the total number of publications (Fig. 2A) or cumulative citations (Fig. 2B). The thickness of the connecting lines between nodes reflects the intensity of co-authorship relationships across nations. The analysis shows that China and the United States are the most leading and collaborative principal points within the network, demonstrating leadership not only in research output but also in international research engagement. China shows extensive bilateral collaboration with countries such as the United States, South Korea, Iran, and Singapore. The United States also maintains strong ties with Canada, Germany, and the United Kingdom.

Figure 2. International collaboration network in aptamer-based cancer research. In panel (A), node size represents the number of publications per country, while in panel (B), node size indicates total citations. In both maps, the thickness of connecting lines reflects the strength of co-authorship links. Cluster colors denote groups of countries with strong collaborative ties. [Click here to view]

The map shows four distinct collaboration clusters. The green cluster, dominated by China and the United States, includes countries such as Canada, Hong Kong, Japan, the Russian Federation, Singapore, and South Korea. The red cluster represents a dense network of European and Middle Eastern countries, including Brazil, Denmark, France, Germany, Iran, Italy, Jordan, Netherlands, Poland, Portugal, Spain, Turkey, and the United Kingdom. The blue cluster comprises Australia, India, Saudi Arabia, and South Africa, while the yellow cluster is centered around Taiwan, Thailand, and Israel. Overall, the results highlight a globally interconnected research landscape, with East Asia, North America, and parts of Europe playing prominent roles in advancing aptamer-related cancer research through international cooperation.

3.6.2. Analysis of author keywords and hotspots prediction

To identify dominant research trends and expect emerging principal themes in the field of aptamers in cancer, a keyword co-occurrence analysis was performed using VOSviewer and Biblioshiny [34,35]. The analysis centered on author keywords to capture themes directly reflective of scholarly emphasis. A thesaurus file was systematically applied to harmonize synonymous terms and ensure consistency in terminology throughout the dataset. Only keywords appearing at least 20 times were retained for the final analysis, thereby emphasizing the most prominent and frequently addressed topics within the literature. Although no formal cluster validation metrics were calculated, keyword clustering was performed using two independent bibliometric software platforms, VOSviewer and Biblioshiny. The resulting thematic clusters were highly consistent across both tools, supporting the stability and reproducibility of the identified structures.

The analysis identified five different clusters of keywords, each cluster represents a central research theme (Table 6 and Fig. 3). The first cluster (red) captures the foundational overlap between aptamer science and core oncological mechanisms (Fig. 3A). It includes terms such as cancer, aptamers, breast cancer, apoptosis, Epidermal Growth Factor Receptor (EGFR) human epidermal growth factor receptor 2 (HER2) siRNA, immunotherapy, and lung cancer, in addition to nanomaterial-related keywords like gold nanoparticles, and nanoparticles.

Figure 3. Most frequently occurring author keywords (≥20 occurrences) in aptamer-based cancer research. (A) Network visualization map created using VOSviewer. (B) Conceptual structure map generated with Biblioshiny. [Click here to view]

Table 6. Most frequent author keywords (≥20 occurrences) in aptamer-based cancer research. Keywords are grouped into thematic clusters based on co-occurrence patterns, reflecting major research areas, and emerging trends.

Keyword	Occurrences	Cluster
Apoptosis	29	1
Aptamers	1,035	1
Breast cancer	89	1
Cancer	109	1
EGFR	21	1
Gold nanoparticles	30	1
HER2	20	1
Immunotherapy	28	1
Lung cancer	49	1
Nanoparticles	96	1
siRNA	31	1
AS1411	86	2
Colorectal cancer	30	2
Doxorubicin	77	2
Fluorescence	36	2
Glioblastoma	22	2
g-quadruplex	28	2
Nucleolin	56	2
Photodynamic therapy	22	2
Targeted drug delivery	221	2
Aptasensor	26	3
Biomarker	23	3
Biosensor	38	3
Cancer therapy	39	3
DNA aptamers	86	3
Ovarian cancer	35	3
Self-assembly	24	3
CTCs	50	4
EpCAM	20	4
Prostate cancer	46	4
RNA aptamers	45	4
SELEX	162	4
Exosomes	24	5
GO	20	5
Liposomes	22	5
PTT	20	5

The second cluster (green) revolves around drug delivery systems and molecular targeting approaches. Keywords include AS1411, colorectal cancer, doxorubicin, fluorescence, glioblastoma, g-quadruplex, nucleolin, photodynamic therapy, targeted drug delivery. This suggests a heavy research focus on functionalizing aptamers for therapeutic applications, particularly those involving nucleolin-targeting strategies, chemotherapeutic payloads, and photo-activated modalities. Aptamer–drug conjugates and their integration with tumor-targeting ligands are key hallmarks of this research area.

Cluster three (blue) represents the growing interest in diagnostics and biosensor technologies. It includes terms such as aptasensor, biomarker, biosensor, cancer therapy, DNA aptamers, ovarian cancer, and self-assembly.

The fourth cluster (yellow) focuses on cellular-level applications and selection techniques. It includes CTCs, EpCAM, prostate cancer, RNA aptamers, and SELEX. This group reflects the advancement of aptamer-based methods for identifying and isolating cancer-specific cells, particularly in the context of liquid biopsies.

Finally, the fifth cluster (violet) represents an emerging frontier that combines aptamers with novel nanocarrier systems and phototherapy. This group includes terms such as exosomes, GO, liposomes, and photothermal therapy (PTT). The integration of aptamers with advanced materials and therapeutic strategies reflects a shift toward multifunctional systems capable of simultaneous diagnosis and treatment (theranostics) and a deeper interest in noninvasive, targeted modalities.

To further explore the intellectual structure of these keywords, a conceptual structure map (Fig. 3B) was generated using Multiple Correspondence Analysis. This map groups keywords based on their semantic proximity and co-occurrence profiles [35,48]. The results reaffirmed the clusters found in the network visualization obtained from VOSviewer.

3.6.3. Thematic map analysis

We used Biblioshiny to build a thematic map based on author keyword co-occurrence, providing insight into the field’s intellectual structure (Fig. 4). This visualization provides a two-dimensional representation of the major research themes, with the x-axis (centrality) indicating a theme’s significance within the broader field, and the y-axis (density) reflecting its level of internal cohesion or developmental maturity. The resulting map categorizes themes into four distinct quadrants: motor themes, niche themes, emerging or declining themes, and basic or transversal themes. This classification facilitates a nuanced understanding of both well-established research domains and those that are newly emerging or undergoing transformation within aptamer-based cancer research [49]. The basic themes quadrant included highly central and established terms such as aptamers, SELEX, cancer, and nanoparticles, representing the foundational structure of the field. The motor themes quadrant, typically indicating well-developed and impactful domains, has minimal representation, implying a continuous evolution of primary research motivations. The niche themes quadrant contained CTCs, exosomes, biosensors, and fluorescence, indicating specialized yet thoroughly formed subjects with robust internal cohesiveness. The quadrant of emerging or declining themes highlighted apoptosis and peptide aptamer, signifying domains with diminished development and prominence that may reflect either nascent or receding research interests.

Figure 4. Thematic map of author keywords in aptamer-based cancer research, constructed using Biblioshiny based on keyword co-occurrence. The x-axis (centrality) represents a theme’s relevance to the broader field, and the y-axis (density) indicates its internal cohesion or development level. Quadrants are motor themes (developed and important), niche themes (specialized), basic themes, and emerging or declining themes. Bubble size reflects keyword frequency. [Click here to view]

3.6.4. Temporal trends and citation impact of author keywords

To further understand the development and research momentum of aptamer-related cancer topics, we used two complementary bibliometric approaches. The first method involved generating an overlay visualization map using VOSviewer, which displays the average publication year of author keywords (Fig. 5A). In this visualization, each term is color-coded along a gradient from blue to yellow, with yellow tones representing the most recently emerging topics. Core terms such as “aptamers,” “cancer,” and “SELEX” appear in darker hues, reflecting their long-standing prominence in the literature. In contrast, emerging topics like “exosomes,” “immunotherapy,” “AS1411,” and “nucleolin” are highlighted in yellow, suggesting their increasing relevance in recent years. This temporal distribution provides insights into the research field’s chronological development and indicates which areas are currently gaining traction.

Figure 5. Temporal and citation-based visualization of author keyword evolution. (A) Overlay visualization map: Node size corresponds to keyword frequency, and color gradient (blue → yellow) indicates the average publication year, revealing the chronological progression of research themes. (B) Trend topic timeline: Displays the lifespan of major author keywords over 2005–2024, with bar length representing the duration of active research focus and color intensity denoting the peak activity period. (C) Normalized citation overlay map: Adjusted for publication year to compare citation impact across time. Node size represents normalized citation count, and the color scale (dark blue → bright yellow) indicates relative influence. [Click here to view]

Another method was applied using the Biblioshiny interface of the Bibliometrix package to investigate the trend topic timeline (Fig. 5B). This trend map visually represents the lifespan and intensity of key author keywords based on their frequency and year of occurrence. Foundational terms such as “aptamers,” “cancer,” and “targeted drug delivery” show consistent presence across the timeline, indicating their centrality and continuity in the field. Meanwhile, more recent interest has shifted toward “exosomes,” “immunotherapy,” “AS1411,” and “CTCs,” reflecting a broadening of research focus toward molecular diagnostics, delivery systems, and therapeutic targeting. Notably, “fluorescence” and “biosensors” have also emerged as sustained areas of interest, especially in the context of detection and monitoring platforms. The clear progression of terms from niche to mainstream reflects the field’s dynamic nature and the gradual adoption of new biomedical innovations.

3.6.5. Analysis of all keywords

A cluster density map was generated using VOSviewer to visualize the distribution and thematic relationships of all keywords extracted from titles and abstracts (Fig. 6). Applying a minimum occurrence threshold of 50 allowed for the inclusion of 314 terms out of 16,728 analyzed. The map shows a color gradient where warmer tones (red and orange) signify higher frequency and research intensity, while cooler tones (green and blue) indicate lower density. Three major thematic regions emerged: one densely populated cluster centers on core concepts such as “aptamers,” “chemistry,” “diseases,” and “diagnosis,” reflecting sustained focus on aptamer development and diagnostic utility. A second cluster is anchored around “drug delivery system,” “nanoparticles,” “apoptosis,” and related therapeutic terms, highlighting the integration of aptamers in drug delivery and cancer treatment. The third area groups molecular and cellular biology themes, including “binding affinity,” “human cell,” and “protein expression,” emphasizing mechanistic and translational research. This mapping illustrates the multidimensional landscape of aptamer-based cancer research, capturing both established and evolving focal points across disciplines (Fig. 6).

Figure 6. Cluster density visualization of all keywords derived from titles and abstracts. The map groups frequently co-occurring terms into color-coded clusters. Red indicates chemistry and diagnostic applications, green emphasizes drug delivery and therapeutic evaluation, while blue represents molecular interactions and cell-based models. Node size reflects term frequency, while spatial proximity and color reflect thematic relationships. [Click here to view]

4. DISCUSSION

Aptamers have emerged as valuable and promising molecular tools in cancer research due to their high specificity, minimal immunogenicity, and can be easily chemically modified. These single-stranded oligonucleotides can adopt distinct three-dimensional conformations that enable selective binding to diverse targets, including proteins, small molecules, and whole cells. Their promise encompasses diagnostics, therapies, targeted drug delivery, and biosensor technologies, rendering them progressively appealing options or complements to antibodies in oncology [2,3]. Aptamers like AS1411 and their conjugated delivery systems have demonstrated significant efficacy in preclinical and translational models, highlighting their importance in precision oncology [50]. This study integrates a quantitative bibliometric mapping of the global aptamer–cancer research landscape with a thematic review derived from author keyword clusters, providing both empirical evidence of research trends and interpretive insights into emerging thematic directions.

Bibliometric analysis functions as an effective method to quantitatively map scientific advancement, pinpoint significant themes, and uncover global trends within a study domain. In rapidly advancing fields such as cancer therapies and molecular diagnostics, bibliometric analyses facilitate the synthesis of extensive literature into practical insights by emphasizing publishing patterns, significant contributions, collaboration networks, and upcoming frontiers [36,48,49]. Considering the interdisciplinary and rapidly evolving landscape of aptamer-based cancer research, a systematic bibliometric analysis is both timely and essential to evaluate the intellectual progress and strategic trajectory of the discipline. We examined the global output on aptamers in cancer research utilizing the Scopus database. This database was chosen because of its strict indexing criteria, comprehensive coverage of peer-reviewed journals, and effective citation tracking. The inclusion of high-impact journals and comprehensive information in Scopus facilitated precise mapping of authorship, institutional productivity, and keyword trends. This analysis offers a detailed examination of research productivity, international collaborations, and topic development, facilitating future planning and strategic investment in aptamer-based cancer innovation.

The bibliometric analysis from 2005 to 2024 indicates substantial expansion in aptamer research, characterized by a steady increase in annual publication volume. Most studies were published after 2017, aligning with the increased utilization of aptamers in drug delivery, biosensing, and nanomedicine. The significant citation count and elevated h-index of pivotal papers indicate the scientific and clinical importance of this field. Leading journals in this field, all classified in the Q1 rank (e.g., Analytical Chemistry, Biosensors, and Bioelectronics), underscore the field’s significant influence and methodological consistency.

China stands out as the leading contributor, producing nearly half of all publications in the field, followed by the United States, Iran, and South Korea. While China leads in volume, the United States demonstrates a higher citation-per-document rate, suggesting a concentration of high-impact contributions. Strong international collaborations, particularly between China and the United States, have accelerated the global dissemination of aptamer research. Bibliometric mapping revealed distinct regional clusters reflecting shared scientific priorities and complementary research strengths, which are crucial for sustaining innovation and advancing clinical translation of aptamer-based technologies. While intra-regional collaborations within Asia, Europe, and North America enhance specialization and coordination, limited cross-regional integration may constrain the exchange of expertise and hinder the development of unified research standards. Enhancing inter-continental collaborations could facilitate methodological standardization, encourage diversity in research methodologies, and expedite global advancements in aptamer-based cancer therapies.

The thematic map analysis (Fig. 4) provides a structured overview of the conceptual organization and maturity of research themes within the field of aptamer-based cancer studies. In the basic themes quadrant, we observe core foundational topics such as “aptamers,” “SELEX,” “cancer,” and “nanoparticles.” These themes form the conceptual backbone of the field and represent the essential components in aptamer technology and its integration into cancer. Their location in this quadrant suggests that while these topics are central and frequently referenced, their internal structure may still be under expansion, indicating significant room for methodological refinement and broader interdisciplinary applications [6]. The motor themes quadrant, typically represents mature and influential areas. However, in this map, no themes are currently positioned within this quadrant, implying a potential opportunity for growth rather than saturation. Themes such as targeted therapy and advanced diagnostic tools might evolve into this quadrant as more translational and clinical research develops [2,20]. The niche themes quadrant highlights specialized and well-developed topics that are relatively isolated from the core field. This includes keywords such as “CTCs,” “biosensor,” “fluorescence,” and “exosomes.” These themes are technically advanced and have well-established methodologies, especially in diagnostic and imaging applications. However, their limited integration with broader research clusters may reflect their specialization or the early-stage nature of cross-disciplinary adoption [51,52]. In contrast, the emerging or declining themes quadrant includes topics such as “apoptosis” and “peptide aptamer.” These themes have low centrality and density, which in bibliometric terms indicate limited current representation rather than reduced scientific significance. While apoptosis continues to be a crucial mechanism in cancer treatment, its diminished prominence in research likely indicates a transition toward broader, application-oriented fields such as targeted delivery systems, immunotherapy, and nanomedicine, where apoptosis is examined as a secondary effect rather than a central theme. This bibliometric positioning signifies an advancement in research focus rather than a diminishment in significance. Similarly, the restricted prevalence of “peptide aptamer” may reflect the increasing preference towards nucleic acid-based aptamers, which provide enhanced structural flexibility and synthetic accessibility [53]. Notably, the “targeted drug delivery” cluster, alongside keywords such as “AS1411,” “doxorubicin (DOX),” and “nucleolin” appear in a transitional zone, bordering between basic and motor themes. This placement highlights its growing significance and increasing coherence, positioning it as a rising research front. The prominence of AS1411 and doxorubicin in the literature underscores the ongoing interest in aptamer-based chemotherapeutic delivery systems, particularly those designed to target cell surface proteins such as nucleolin across various tumor models [12]. Collectively, the thematic map illustrates a dynamic and growing research landscape. While some areas remain in early stages of development, others most remarkably those related to drug delivery and diagnostic applications, are characterized with significant growth. These findings suggest valuable opportunities for aligning between specialized diagnostic approaches and more comprehensive therapeutic frameworks, highlighting a promising direction for the advancement of aptamer-based technologies in cancer research.

The temporal trend and citation impact analyses (Fig. 5) provide significant insights into the chronological development and scientific effect of research themes in aptamer-based cancer investigations. These visualizations highlight not only when specific topics emerged but also how their relative importance and impact have shifted over time. The normalized citation overlay map (Fig. 5C) was created to adjust citation counts relative to the year of publication. Which allows a fair comparison of impact across different periods. In this visualization, node size represents normalized citation count, while the color gradient—from dark blue to bright yellow—reflects citation intensity. Keywords such as “AS1411,” “nucleolin,” “targeted drug delivery,” and “exosomes” exhibit high normalized citation values, demonstrating their influence in the literature regardless of their relatively recent emergence. Foundational terms such as SELEX, nanoparticles, and biosensors display moderate normalized citation density, reflecting their established yet plateaued influence. These can be viewed as “transient hotspots,” representing themes that were once central to aptamer research but now show slower citation growth. In contrast, AS1411, nucleolin, and exosomes can be regarded as “sleeping beauties,” having initially limited visibility but later achieving significant citation momentum, underscoring their growing translational relevance in drug delivery and biomarker discovery. Collectively, these findings indicate a thematic transition in aptamer research from methodological development toward application-oriented innovation. The chronological evolution reveals a shift from foundational platform establishment to integration with advanced therapeutic systems such as exosome-based delivery, fluorescence-guided imaging, and immune-targeting constructs. Together, these emerging directions highlight the field’s movement toward precision and personalized cancer treatment strategies. Within this broader transition, “exosomes” have emerged as a particularly promising theme, as evidenced by their rapid rise in keyword frequency and normalized citation impact. Their inherent role as biocompatible nanocarriers and their integration with aptamer technology for targeted delivery and liquid biopsy applications suggest that exosome-related research will likely define the next phase of aptamer-based cancer innovation. Moreover, their frequent co-occurrence with established terms such as “targeted drug delivery” in the clustering and citation overlay maps highlights how exosome research is evolving from an emerging niche into a central component of the broader aptamer-based therapeutic landscape. This growing integration parallels recent progress in systemic cancer therapy, where biomarker-guided and response-predictive strategies have become increasingly important in optimizing treatment outcomes [54–56]. Aptamer-based systems naturally align with this shift, offering dual diagnostic and therapeutic potential. Current studies demonstrate Aptamer-conjugated Poly(lactic-co-glycolic) acid (PLGA) nanoparticles for delivery, molecular imaging, and immunotherapy modulation of cancer therapeutic drugs [57], while exosome-integrated aptamer platforms are being explored for precision diagnostics and real-time monitoring [52]. Collectively, these trends highlight the translational potential of aptamers as adaptable tools that bridge targeted treatment and predictive oncology.

5. LIMITATION

This study presents a thorough bibliometric analysis of aptamer-based cancer research; nonetheless, some limitations should be recognized. The exclusive use of the Scopus database, the largest abstract and citation repository with robust multidisciplinary coverage that also includes PubMed and a substantial portion of Web of Science records, may introduce source bias by excluding studies indexed solely in other databases. This approach is common in bibliometric research to ensure dataset consistency and tool compatibility; however, future studies could integrate multiple databases to enable sensitivity testing and cross-validation of results.

The restriction to English-language publications may make a potential linguistic bias, as relevant studies published in other languages may have been overlooked. Furthermore, the analyses include original research articles only, thereby excluding conference proceedings, reviews, editorials, and book chapters, which could provide valuable insights. In addition, keyword analysis utilized a custom thesaurus to amalgamate synonyms, a requisite yet subjective procedure that may have impacted clustering results and keyword correlations. The establishment of inclusion thresholds, such as requiring keywords to have a minimum of 20 occurrences, although essential for clarity and manageability, may have unintentionally excluded emerging terms and nuanced research topics that are still evolving in the field. Notwithstanding these constraints, the study offers significant and empirical insights into the structure, dynamics, and global collaboration patterns of aptamer-related cancer research. This study focuses on thematic mapping and hotspot identification rather than detailed keyword lifespan or burst analysis. While trend maps and thematic evolution provide an indirect view of temporal dynamics, in-depth burst detection and rise/decline rate analysis were beyond the current scope and could be addressed in future research.

6. CONCLUSION AND FUTURE PERSPECTIVES

This bibliometric and thematic analysis provides a comprehensive overview of the global research landscape on aptamers in cancer research, highlighting important contributors, theme clusters, and promising research trajectories. The findings indicate a significant transition towards the incorporation of aptamer-based approaches in diagnostics, therapeutics, and nanotechnology. Aptamers have transitioned from specialized molecular tools to multifunctional platforms for targeted drug delivery, biosensing, and imaging. Prominent themes such AS1411, SELEX, targeted treatment, and exosome-based delivery systems highlight the translational potential of the field. Among the rising research themes, “exosomes” emerge as a significant keyword likely to influence the direction of aptamer–cancer research in the next years, as indicated by their swift increase in frequency and normalized citation impact. The absence of well-defined motor themes indicates a continual disparity between experimental progress and clinical application. Funding agencies should prioritize multidisciplinary programs that connect aptamers with exosome-based delivery, immunotherapy, and biosensing, therefore translating these promising fields into clinically applicable discoveries.

Future studies should continue addressing major challenges affecting clinical translation, including aptamer instability, off-target interactions, and pharmacokinetic constraints. Enhancing collaboration among molecular biologists, materials scientists, and physicians is essential for progressing aptamer–nanocarrier systems from preclinical assessment to clinical use. Expanding clinical pipelines and promoting international collaboration and data exchange will further advance innovation and standardization. This study combines quantitative bibliometric mapping with thematic analysis to establish a solid, evidence-based framework for directing future research priorities and expediting the implementation of aptamer-based cancer therapies.

7. ACKNOWLEDGMENT

The authors would like to acknowledge the University of Sharjah, the University of Jordan, and Al-Ahliyya Amman University for their support. This project was funded by the University of Jordan (grant No. 2391) and the University of Sharjah (Competitive grant No: 24010901172).

8. AUTHOR CONTRIBUTIONS

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agreed to be accountable for all aspects of the work. All the authors are eligible to be an author as per the International Committee of Medical Journal Editors (ICMJE) requirements/guidelines.

9. CONFLICTS OF INTEREST

The authors declare that they have no financial or personal relationships with any individuals or organizations that could inappropriately influence their work. There are no professional or personal interests of any nature in any product, service, or company that could be construed as influencing the content or conclusions of this manuscript.

10. ETHICAL APPROVALS

This study does not involve experiments on animals or human subjects.

11. DATA AVAILABILITY

All data generated and analyzed are included in this research article.

12. PUBLISHER’S NOTE

This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.

13. DECLARATION OF GENERATIVE AI AND AI-ASSISTED TECHNOLOGIES IN THE WRITING PROCESS

QuillBot and ChatGPT were used to refine the language and improve readability. The authors thoroughly reviewed and edited all content and take full responsibility for its accuracy and integrity. No figures or images were generated or modified using AI tools.

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