Global trends and characteristics of metal–organic frameworks in cancer research: a machine-learning-based bibliometric analysis

Abstract

Background

Cancer poses a significant health threat, causing millions of deaths annually. Although chemotherapy-based comprehensive therapies are common, their low accuracy and severe side effects limit effectiveness. Metal–organic frameworks (MOFs), with their superior biocompatibility and stability, show great promise for drug delivery and cancer treatment. This study aims to explore the potential and developmental trajectories of MOFs in cancer research through a bibliometric analysis.

Methods

The Web of Science Core Collection was searched for documents from its inception in 2009 to December 31, 2023. We analyzed and visualized document types, countries, institutions, authors, journals, references, and keywords using the Bibliometrix package, dplyr, sankeywheel, term extraction, and ggplot2. Additionally, the Latent Dirichlet Allocation (LDA) algorithm was employed for detailed semantic analysis, uncovering latent thematic distributions.

Results

A total of 7106 authors from 1591 institutions across 45 countries contributed 1955 papers on MOFs in cancer research, published in 327 journals. China leads in research output and international collaboration, with the Chinese Academy of Sciences as the top institution. Lin Wenbin from the University of Chicago is the most influential author, and ACS Applied Materials & Interfaces is the most active journal. MOFs are predominantly studied for breast cancer, followed by lung and liver cancers. Drug delivery remains a focal point for future research.

Conclusions

This study provides a comprehensive overview of the research landscape on MOFs in cancer treatment, offering insights into key trends and future directions, particularly in drug delivery and disease-specific applications.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12672-025-02716-8.

Highlights

1. This study comprehensively explores the development trends and hot research topics of MOFs in cancer research through the combined analysis of bibliometrics and LDA topic modeling for the first time.

2. China has made significant contributions and holds a leading position in MOFs in cancer research.

3. Tumor correlation analysis results indicate that MOFs are most widely used in the field of breast cancer, followed by lung cancer and liver cancer.

4. The future research directions in this field mainly focus on drug delivery and tumor treatment, including photodynamic therapy, photothermal therapy, and immunotherapy.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12672-025-02716-8.

Introduction

Cancer is a type of malignant tumor characterized by abnormal cell differentiation, uncontrolled growth, and invasive metastasis [1]. The incidence of cancer has been rapidly increasing worldwide in recent decades. According to the World Health Organization, cancer is the second leading cause of death globally, with approximately 2 million new cases and 610,000 deaths expected in the United States by 2024 [2]. The current cancer mortality rate has substantially decreased with continuous improvements in early detection technologies and innovations in treatment methods. However, the rising incidence of cancer still imposes a significant economic burden globally and severely affects health-related quality of life. Currently, surgery, radiation therapy, and chemotherapy are considered the standard cancer treatments, but their poor precision, low efficiency, and severe side effects significantly undermine their effectiveness. In recent years, various treatment methods such as immunotherapy, chemodynamic therapy (CDT), and phototherapy have been extensively developed due to their minimal side effects, non-invasiveness, and ease of use, enhancing the effectiveness of cancer treatment and meeting growing clinical demands [3, 4]. However, these treatment strategies still face significant challenges in the cancer treatment process. Recently, the interest in the application of nanomaterials in cancer has grown substantially in recent years, with significant advancements in their use for drug delivery and biomedical imaging, providing new approaches to improving the diagnosis and treatment of tumors [5, 6].

Metal–organic frameworks (MOFs), also known as porous coordination polymers, are three-dimensional materials composed of metal ions (clusters) bridged by organic ligands. They feature large surface areas, ordered crystal structures, good biocompatibility, and excellent chemical stability [7]. MOFs hold significant potential for applications in biochemical sensing, synthetic catalysis, molecular imaging, drug delivery, and cancer treatment [8]. Since 2006, when Férey and colleagues first documented the utilization of MIL-100 and MIL-101 materials from the Lavoisier Institute for the delivery of ibuprofen, there has been substantial progress in the properties of MOFs, including biocompatibility, safety, and targeting capabilities [9, 10]. These advancements over the past two decades can be attributed to significant developments in controlled synthesis and surface functionalization techniques. MOFs can be modularly synthesized under mild conditions by selecting molecular components, allowing for the activation of multiple functionalities within the framework through pre-designed or post-synthesis methods. Besides the inherent imaging capabilities of their organic ligands and metal ions, many MOFs also serve as carriers for contrast agents. For instance, MOFs imaging agents used in tumor diagnosis primarily achieve passive targeting by accumulating in tumors through enhanced permeation and retention effects (EPR) or active targeting by binding MOFs to tumor-specific receptors. In cancer therapy, MOFs can serve as drug carriers to improve the pharmacokinetics and biodistribution of drugs, modulate the uptake and metabolic pathways of drugs in tissues, and increase drug accumulation in tumors, enhancing therapeutic effects and reducing adverse reactions [11]. Therefore, the application of MOFs in cancer diagnosis and treatment is a promising avenue for extensive and in-depth research.

Bibliometrics is the systematic qualitative and quantitative assessment of research publications. It was first defined in 1969 as applying mathematical and statistical methods to compute and analyze various aspects of textual information, thereby elucidating textual processes as well as the nature and trends of disciplinary development [12]. In recent years, bibliometrics has been extensively applied to study the characteristics of academic publications in specific research fields, influential countries, journals, institutions, and authors, as well as influential publications, references, and keywords [13]. With the advent of the significant data era, text analysis and natural language processing have become essential in bibliometric research. The LDA (Latent Dirichlet Allocation) topic model is an unsupervised machine learning technique widely used in natural language processing [14]. The LDA model can extract topics from large amounts of textual data and then further analyze how these topics interact and evolve across different documents [15]. This study will comprehensively explore the development trends and emerging research trends of MOFs in the field of cancer through bibliometric methods and topic model analysis, providing researchers, clinicians, and policymakers with a thorough overview of the current knowledge and understanding of MOFs in cancer.

Materials and methods

Data collection

The data were extracted from the Web of Science Core Collection (WOSCC) database (https:// clarivate.com/) on April 26, 2024. The WOSCC is one of the most widely used academic databases, as it is one of the most expansive electronic repositories of scientific literature worldwide. In addition, it offers reliable and detailed bibliometric analysis data for many leading journals. Compared to other research databases like Scopus and PubMed, the Web of Science Core Collection (WOSCC) offers several distinct advantages [16]. First, it demonstrates comprehensive coverage across both the natural and social sciences, with particular strength in high-impact journals within specific disciplines. Secondly, WOSCC is distinguished by its frequent data updates, which ensure timely access to the most recent research findings. Additionally, the citation analysis tools offered by WoSCC enable researchers to gain a deeper understanding of the interconnections and impact within the scholarly literature.

A comprehensive search was conducted from the establishment of the database in 2009 until December 31, 2023. This search employed a structured retrieval strategy (Supplementary Table 1), utilizing the keywords “Metal–Organic Framework” and “cancer.” To enable a more focused analysis of the literature, only articles and review articles published in English were included (Fig. 1). A complete record and cited references were extracted from relevant publications and saved in plain text format for further research. In addition, we downloaded the “Analyze Results” data table from WOSCC.

Fig. 1.

Flowchart of the screening process

Data analysis and visualization

Software tools and respective functions

The software tools used for bibliometric analysis included Bibliometrix (version 4.030) and R (version 4.2.3). Additionally, the online bibliometric website (https://bibliometric.com/) was used to visualize international collaboration. Bibliometrics is a distinctive open-source tool for performing comprehensive scientific mapping analysis, which includes data import, format transformation, data cleansing and organization, descriptive statistics, co-occurrence matrices, data normalization, and mapping [17]. To create social network maps, we analyzed document types, years, authors, countries, institutions, and keywords. In Bibliometrix, extraction methods involve extracting authors from the AU field, institutions from the AU_UN field, countries from the AU_CO field, the year of publication from the PY field, and citations from the TC field. We applied filtering steps to reduce noise and to ensure that the extracted topic accurately reflects the focus of the topic stated by the author. The keywords of this study were extracted from the DE field. Initially, the retrieved articles from the databases were exported to Biblimetrix for conversion into Bibliometrix R Data format for subsequent analysis. Finally, we used R (version 4.2.3) to perform a descriptive bibliometric analysis and generate a comprehensive document matrix. We grouped and summarized this data using the “dplyr” package (version 2.5.0) to calculate annual publication counts, citation counts, participating countries, and research areas. The visualization part was primarily conducted using the “ggplot2” package (version 3.5.1).

Analysis of national and institutional influence and collaboration of MOFs in cancer

To assess the academic influence of different countries and institutions in this field, we calculated the H-index of the top 10 countries and institutions and analyzed the corresponding G-index, M-index, the publication year of the first paper (PY_start), total citation count (TC), and the number of publications, using the Hindex function in the Bibliometrix package. In addition, we extracted unique country names from the list separated by semicolons in each AU_CO record to ensure that no duplicate country names were present within the same entry. We selected the countries with the top 10 H-index values. We used the “sankeywheel” package (version 0.1.0) to allocate distinct colors to each country, enriching the visualization and promoting an intuitive grasp of the global research network’s interconnections.

Analysis of the themes categories evolution of MOFs in cancer

To better understand the current research hotspots and future development directions of MOFs in cancer in various countries, we compared the similarities and differences in MOFs in cancer in different countries. We extracted the thematic categories from the “DE” in the literature list. We employed the “term extraction” package to identify thematic words pertinent to various countries or regions, concurrently undertaking the processes of cleaning and deduplication. Specifically, we conducted a manual review to consolidate related terms, drawing upon contextual and semantic similarities. Each extracted term was accompanied by a list of synonyms, delineated by semicolons, which were subsequently integrated into a unified term. The latent Dirichlet Allocations (LDA) topic model is an unsupervised learning algorithm with document-topic and topic-word probability distributions. By analyzing word information in unstructured text data, the model abstracts and clusters topics in a series of documents, thus realizing text classification and exploring subject patterns in the corpus. This approach delineates current research frontiers and surfaces latent trajectories, guiding future scholarly inquiry. In this study, we employed the “tm” package (version 0.7–14), the “topicmodels” package (version 0.2–17), and the “LDAvis” package (version 0.3.2) for the analysis of Latent Dirichlet Allocation (LDA) topic modeling. We utilized the Gibbs sampling method to analyze the top 20 themes categories.

Results

Overview of trends and evolution of MOFs in cancer

A total of 2167 publications were retrieved from the Web of Science Core Collection (WOSCC) database. The selection criteria were restricted to articles and reviews, with the language limited to English. Ultimately, 1955 relevant articles were identified, comprising 1735 original research articles and 220 review articles, with an H-index of 133.The annual growth rate is 54.95%, and the average citations per publication is 44.47. Figure 2A displays the number of publications and citations related to MOFs in cancer, from 1 publication in 2009 to 460 publications in 2023. The number of publications grew slowly, with no more than ten documents per year before 2015. From 2015 to 2023, the number of publications increased rapidly, the accomplishment was that the number of publications reached 460 in 2023. Due to the time accumulation required for citation analysis, excellent research in emerging fields may only partially demonstrate its value due to the relatively short time. Therefore, evaluations based on citation analysis may have a time delay. From the perspective of the number of participating countries, the increase from 1 country in 2009 to 31 countries in 2023 indicates that MOFs in cancer research is being valued and attracting widespread global attention (Fig. 2B).

Fig. 2.

Trends and evolution of MOF-related cancer research from 2009 to 2023. A Annual trends in the number of publications and total citations related to MOFs in cancer research. The bar chart shows publication counts, while the line graph indicates total citation volume, reflecting the growing impact of this research field. B Growth in the number of countries participating in MOF-based cancer research over time, indicating increasing global engagement in the field. C Expansion in the number of Web of Science (WOS) research categories associated with MOF-based cancer studies, showing a broadening of interdisciplinary applications. The fitted regression line demonstrates a strong upward trend (R² = 0.91, P < 0.001). D The top ten most productive WOS subject categories in MOF-related cancer research. The line chart depicts the yearly increase in publication counts across key disciplines

WOS research areas, assigned by Clarivate Analytics, were used to classify the research papers. Each paper can be classified into at least one research area in the WOSS database [18]. In this study, the number of research areas covered by the MOFs in cancer increased from 3 in 2009 to 27 in 2023(Fig. 2C). The top ten most productive research areas were Chemistry, Materials Science, Biochemistry and Molecular Biology, Pharmacology and Pharmacy, Physics, Science and Technology, Biophysics, Biotechnology and Applied Microbiology, Electrochemistry, and Engineering, which represented 3476 of the 3687 publications, accounting for approximately 94.28% of the total. The annual evolution of the ten most productive areas of MOFs in cancer research is shown in Fig. 2D, which illustrates changes in the focus areas in this field. Before 2015, the dominant research areas were “Chemistry” and “Materials Science,” with “Science and Technology” increasing rapidly in popularity in later years, becoming a gradual increase in the MOFs literature output field by 2015. In recent years, interdisciplinary disciplines such as Engineering and Physics have begun to join the field of research.

Analysis of national publication volume and collaboration of MOFs in cancer

National publication counts were analyzed to investigate the countries/regions contributing the most in this field. The results show that Asia (90.73%) occupied an absolute leading position in terms of the number of publications, followed by Europe (3.64%), the Americas (3.48%), Africa (1.28%) and Oceania (0.87%) (Supplementary Fig. 1). According to the search results, all the documents were obtained from 45 countries. Table 1 lists the top 10 countries and number of publications (NP), number of citations (NC), Single Country Publications (SCP), Multiple Country Publications (MCP), Multiple Country Publications Ratio (MCP_Ratio), publication year of the first paper (PY), G-index, M-index, the sorted by the H-index. Notably, China has the highest number of publications in this field (1542, H-index = 109), followed by the USA (61, H-index = 54), Iran (128, H-index = 26), Singapore (10, H-index = 24) and India (68, H-index = 20). Figure 3A shows the number of published papers and citations in each country over time. The USA and Korea were the earliest to start research in MOFs in cancer, with the first relevant literature published in 2009 and 2010. China started its research in 2011 and has made rapid progress recently.

Table 1.

Top 10 Countries in the field of MOF in cancer

Country	NP	NC	SCP	MCP	MCP_Ratio	PY	H-index	G-index	M-index
China	1542	50764	1367	175	0.113	2010	109	167	7.79
USA	61	14394	44	17	0.279	2013	54	119	4.91
Iran	128	2085	90	38	0.297	2014	26	41	3.25
Singapore	10	2749	4	6	0.591	2014	24	29	2.4
India	68	1456	45	23	0.338	2012	20	37	2.22
Korea	27	4694	18	9	0.333	2015	16	33	1.07
Spain	8	1240	5	3	0.375	2015	16	20	1.45
United Kingdom	11	937	5	6	0.545	2012	16	20	1.78
Germany	8	1805	5	3	0.375	2013	13	15	1.44
Israel	14	1031	12	2	0.143	2016	13	14	1.63

Fig. 3.

National publication output and international collaboration of MOFs in cancer from 2009 to 2023. A Bubble plot illustrating the annual number of publications and total citation counts for the top 10 contributing countries. Bubble size represents the number of articles, while color intensity indicates the total citation volume. B Violin plot showing the distribution of standardized citation counts (log-transformed) for each country. The width of each violin reflects the density of the data, and the embedded boxplots indicate medians and interquartile ranges. C Ridgeline density plots comparing the citation distribution (log-transformed) across countries, highlighting differences in research impact within each national cohort. D Chord diagram displaying international collaboration among countries with more than ten co-authored publications. The width of each link denotes the frequency of collaboration, illustrating the strength and direction of global research partnerships

In order to eliminate the effect of the number of publications on the number of citations, this study standardized the number of citations by the number of publications to infer each country’s objective influence in the MOFs field in cancer. It is worth noting that although the USA and Singapore have fewer publications in this field than China, their article influence occupies an essential global position. In addition, the United Kingdom and Israel have a strong international influence in this field (Fig. 3B). The results of a further citation density graph show that the density curve of China shows a clear peak, indicating that most academic citations are concentrated in a relatively high interval (Fig. 3C). This means China has a broad research base and a high citation frequency in this field. The USA has a broader density curve, showing a wider distribution of citations. The peak is less prominent than China’s but covers a more comprehensive range of citations. In other countries, such as Iran, Singapore and India, the curve is flatter, indicating that their academic citations are more uniform and there are no prominent peak areas.

MCP revealed the publication number of co-authors from different countries/regions. Although China had the highest MCP (n = 175), its MCP ratio (= MCP/articles) was only 11.3%. Singapore has the highest MCP ratio (60%), followed by the United Kingdom (54.5%), Spain (37.5%) and Germany (37.5%) (Supplementary Fig. 2A). In order to further the cooperation relationship between countries, we draw a map of the national cooperation network, in which the size of nodes represents the number of publications. The density of connections between nodes represents the intensity of cooperation. The results show that China collaborated closely with the USA, whereas research collaborations among other countries were scattered (Supplementary Fig. 2B). In order to explore the intensity of national cooperation further, we extracted the author’s country and further analyzed the cooperation network diagram of countries with more than ten cooperation times. The result shows that China has the closest cooperation with the United States, followed by Singapore, Australia, and Iran, further indicating that China is leading in international cooperation (Fig. 3D).

Analysis of the institution and impact of authors of MOFs in cancer

The number of publications from various institutions was analyzed to explore institutions contributions to MOFs in cancer. Metal–organic frameworks in cancer research were conducted at approximately 1591 institutions worldwide. As shown in Fig. 4A, 17 research institutions are from China, one is from the USA, one is from Egypt, and one is from France. With 265 articles published, the Chinese Academy of Sciences ranked first, followed by the Changchun Institute of Applied Chemistry (94) and the University of Chinese Academy of Sciences (78). Table 2 lists the top 10 institutions and G-index, M-index, the publication year of the first paper (PY), Country, total citation count (TC), and the number of publications sorted by the H-index. Notably, the Chinese Academy of Sciences has the highest number of publications in this field (265, H-index = 74), followed by Changchun Institute of Applied Chemistry (94, H-index = 45), University of Chinese Academy of Sciences (78, H-index = 38), University of Science and Technology of China (70, H-index = 34), and Wuhan University (71, H-index = 33).

Fig. 4.

Institutional and author contributions of MOFs in cancer from 2009 to 2023. A Top 20 most productive institutions in the field, ranked by the number of publications. B Top 20 most prolific authors based on publication volume

Table 2.

Top 10 institutions in the field of MOF in cancer

Sources	Articles	TC	PY_start	Country	h_index	g_index	m_index
Chinese Academy of Sciences	265	18232	2011	China	74	128	5.29
Changchun Institute of Applied Chemistry	94	6387	2012	China	45	79	3.46
University of Chinese Academy of Sciences	78	5207	2012	China	38	72	2.92
University of Science and Technology of China	70	4235	2011	China	34	65	2.43
Wuhan University	71	9064	2015	China	33	71	3.30
Shanghai Jiao Tong University	61	2401	2016	China	31	48	3.44
Nankai University	43	3822	2016	China	30	43	3.33
Fudan University	61	2365	2016	China	27	48	3.00
Centre national de la recherche scientifique	38	5282	2010	France	26	38	1.73
University of Chicago	40	4778	2016	USA	26	40	2.89

In order to discern the most prolific authors, we employ researcher profiles in WOSS to rank them according to the total number of articles. 7106 authors produced the 1955 selected publications in the field of MOFs in cancer. There are 9 Single-authored documents, and the proportion of international co-authors is 25.79%. Figure 4B and Table 3 show that Tang Bo from Shandong Normal University was the most productive author, with 26 articles published and a 98 H-index. Following behind were Pan, Wei from Fujian Medical University (24 articles, H-index = 50), Xie, Zhigang from the University of Science and Technology of China (22 articles, H-index = 70), and Li, Na from Shandong Normal University (22 articles, H-index = 61). It is worth noting that seventeen of the twenty authors are from China, indicating that China is also a leader in this field.

Table 3.

Top 10 authors in the field of MOF in cancer

Researcher	Articles	H-Index	Country	Institution
Tang, Bo	26	98	China	Shandong Normal University
Pan, Wei	24	50	China	Fujian Medical University
Xie, Zhigang	22	70	China	University of Science and Technology of China
Li, Na	22	61	China	Shandong Normal University
Dong, Yu-Bin	22	64	China	Shandong Normal University
Zhang, Zhi-Hong	21	58	China	Beijing University of Technology
Lin, Wenbin	20	124	USA	University of Chicago
He, Linghao	19	56	China	Zhengzhou University of Light Industry
Qu, Xiaogang	18	69	China	Chinese Academy of Sciences
Meng, Xianwei	18	37	China	Chinese Academy of Sciences

Analysis of publication quantity and journal impact of MOFs in cancer

The retrieved data were published in 327 different journals. Among them, 146 (44.65%) journals published only one article, 130 (39.76%) journals published two-ten articles, and 51 (15.60%) journals published more than ten studies (Supplementary Fig. 3). Table 4 lists the top 10 journals and G-index, M-index, the publication year of the first paper (PY), Country, total citation count (TC), the number of publications, latest impact factors (IF) and Journal Citation Reports (JCR) sorted by the H-index. ACS Applied Materials & Interfaces is the most productive journal, with 137 articles published and 55 H-index. Following behind were Advanced Functional Materials (53 articles, H-index = 36), Biomaterials (41 articles, H-index = 32), and Advanced Materials (34 articles, H-index = 27). The average IF with the top 10 journals was 14.76, all in the first quartile (Q1) of the JCR.

Table 4.

Top 10 journals in the field of MOF in cancer

Sources	Articles	TC	PY_start	Country	IF/JCR	h_index	g_index	m_index
Acs Applied Materials & Interfaces	137	7288	2014	USA	9.5/Q1	55	81	5
Advanced Functional Materials	53	5100	2016	Germany	19/Q1	36	53	4
Biomaterials	41	3772	2016	Netherland	14/Q1	32	41	3.56
Advanced Materials	34	5663	2016	Germany	29.4/Q1	27	34	3
Journal Of Materials Chemistry B	66	1932	2013	UK	7.0/Q1	27	42	2.25
Acs Nano	38	6492	2014	USA	17.1/Q1	26	38	2.36
Biosensors & Bioelectronics	40	1991	2016	Netherland	12.6/Q1	26	40	2.89
Analytical Chemistry	46	2002	2014	USA	7.4/Q1	25	44	2.27
Journal Of The American Chemical Society	30	5485	2014	USA	15/Q1	25	30	2.27
Angewandte Chemie-International Edition	28	3275	2016	Germany	16.6/Q1	24	28	2.67

Analysis of co-cited references of MOFs in cancer

The top 10 most globally cited documents are listed in Table 5. “Porous metal- organic-framework nanoscale carriers as a potential platform for drug delivery and imaging” published by Horcajada P and his colleagues in 2010 is the most cited documents with a total of 3,476 citations. Five of the top 10 documents came from the China, three from USA, one from France and one from Spain. The Normalized Total Citation (TC) metric offers a comparative assessment of each paper's impact by adjusting the total citation count relative to the most highly cited paper within the dataset. This normalization facilitates a more equitable comparison of citation performance across papers published in varying years, thereby reflecting their relative influence within the field of MOFs in cancer research. The study by Horcajada et al. [19] published in Nature Materials is utilized as the reference point, possessing a normalized TC value of 1, due to its status as the most highly cited work, with a total of 3476 citations. In contrast, the study conducted by Langer et al. [20] and published in ACS Nano demonstrates a significantly higher normalized TC value of 33.12. This suggests a substantially elevated citation rate per annum, attributable to its recent publication and swift influence within the field. Similarly, the research by Wu et al. [8] in Advanced Materials exhibits a normalized TC of 13.21, underscoring its considerable impact since its release. In comparison, other studies, such as those by Zhuang et al. [21] in ACS Nano and Li et al. [22] in ACS Nano, present normalized TC values of 2.89 and 5.29, respectively, indicating a moderate impact when compared to the baseline paper.

Table 5.

Top 10 co-cited references related to MOF in cancer

Paper	DOI	Country	TC	TC per year	Normalized TC
Horcajada P, 2010, Nat Mater	10.1038/NMAT2608	France	3476	231.73	1
Langer J, 2020, Acs Nano	10.1021/acsnano.9b04224	Spain	2041	408.2	33.12
Wu Mx, 2017, Adv Mater	10.1002/adma.201606134	China	1599	199.88	13.21
Zhuang J, 2014, Acs Nano	10.1021/nn406590q	USA	680	61.82	2.89
Li Sy, 2017, Acs Nano	10.1021/acsnano.7b02533	China	641	80.13	5.29
Park J, 2016, J Am Chem Soc	10.1021/jacs.6b00007	USA	640	71.11	4.06
Lan Mh, 2019, Adv Healthc Mater	10.1002/adhm.201900132	China	618	103	8.63
Lu Kd, 2014, J Am Chem Soc	10.1021/ja508679h	USA	576	52.36	2.45
Lan Gx, 2018, J Am Chem Soc	10.1021/jacs.8b01072	China	511	73	6.58
Hu Yh, 2017, Acs Nano	10.1021/acsnano.7b00905	China	496	62	4.1

Research hotspots and frontiers of MOFs in cancer

Identifying research hotspots and frontiers is crucial for comprehending the evolution and direction of a scientific field. Key themes and shifts in research can be elucidated by analyzing recurring keywords. There were 3736 Authors’ Keywords collected in this research. The Latent Dirichlet Allocation model, was chosen with five topics for its coherence and interpretability. We employed Gibbs sampling for its efficacy with categorical data, which provided an intertropical distance map that visualizes the latent topics identified within a dataset focused on material science and medical applications. Topic 1: Nanoparticle-Mediated Therapies in Oncology. This topic is dominated by terms like “therapy,” “nanoparticles,” “photodynamic,” “tumor,” and “drug delivery,” which collectively suggest a focus on using nanotechnology in cancer treatment (Fig. 5A). Topic 2: Synthesis and Design of Drug Delivery Platforms, featuring keywords such as “synthesis,” “release,” “adsorption,” and “coordination” (Fig. 5B). Topic 3: Metal–Organic Frameworks (MOFs) in Cancer Treatment. This topic is distinct in its emphasis on “metal–organic frameworks” and their application in cancer therapy. Key terms such as “apoptosis,” “resistance,” and “lung cancer” imply a dual focus on understanding the cellular mechanisms of cancer and overcoming drug resistance (Fig. 5C). Topic 4: Mesoporous Materials for Drug Delivery. The isolated position of Topic 4 on the map, along with terms like “mesoporous,” “silica,” and “nanocarriers,” underscores a specialized niche in material science. It focuses on leveraging the unique properties of mesoporous materials for drug delivery applications (Fig. 5D). Topic 5: Graphene-Based Sensors and Detection Systems. Distinguished by terms such as “detection,” “graphene,” “biosensor,” and “electrochemical,” Topic 5 reveals a significant trend towards developing advanced sensors using nanomaterials (Fig. 5E). Figure 5F demonstrates the top 20 keywords sorted by occurrence frequency. The keyword “Metal–Organic Framework” was used most frequently, with 621 occurrences, followed by “Photodynamic Therapy” (n = 159), “Drug Delivery” (n = 144), “Photothermal Therapy” (n = 77), and “Cancer Therapy” (n = 65).

Fig. 5.

Intertopic distance maps and keyword analysis based on Latent Dirichlet Allocation (LDA) modeling of MOFs in cancer from 2009 to 2023. The intertopic distance maps (left) display the relative position and prevalence of each topic, while the right panels show the top 30 most relevant terms contributing to the semantic structure of each topic. A Topic 1 accounts for 20.2% of all tokens and focuses on graphene-based materials for sensing and detection. B Topic 2 comprises 20.1% of tokens and centers on MOF-based drug delivery systems and nanoparticle synthesis. C Topic 3 represents 20.0% of the dataset and focuses on nanoparticle-mediated phototherapy for cancer. D Topic 4, covering 19.9% of tokens, relates to the design and functionalization of MOFs for biomedical applications. E Topic 5 accounts for 19.7% of the corpus and is centered on drug delivery platforms and functional nanocarriers. F The bar chart displays the top 20 most frequently occurring keywords across the entire corpus, indicating major research themes and hotspots in MOF-related cancer studies. Bar lengths represent the total number of keyword occurrences

The analysis results of subject words further extracted from keywords show that in the early stage of the development of this field, the main themes are concentrated on Targeted Drug Delivery, Magnetic Metal − organic Framework, and Anticancer Drug Delivery. In recent years, it has mainly focused on Enhanced Chemo Dynamic Therapy, Bimetallic Metal − organic Framework and Breast Cancer Treatment. It showed that themes evolve dynamically over time (Fig. 6A). Tumor correlation analysis results indicate that MOFs is most widely used in the field of tumors for breast cancer (187), followed by lung cancer (79), liver cancer (43), colorectal cancer (39), and prostate cancer (31) (Supplementary Fig. 4). After conducting a relevance analysis of the thematic content, we found that the theme terms can be divided into three periods: 2009–2014, 2015–2018, and 2019–2023(Fig. 6B). We further extracted the TOP10 theme terms for each period. From 2009 to 2014, 15 papers were published, focusing mainly on material exploration in catalytic activity, coordination polymers, and copper cyanide. In 2015–2018, the papers increased to 293, focusing on developing anticancer activity, coordination polymers, and controlled-release drug materials. In the last five years (2019–2023), the number of papers has increased significantly, with 1647 papers published. These papers mainly focus on tumor therapy, covering various aspects such as photodynamic therapy, photothermal therapy, chemotherapy, and immunotherapy.

Fig. 6.

Thematic evolution analysis of MOFs in cancer from 2009 to 2023. A Heatmap showing the temporal trends of key research themes. Color intensity represents the relative prevalence of each theme across publication years, indicating emerging and expanding focus areas over time. B Correlation matrix of theme categories across years. The size and color of the circles represent the strength and direction of correlations between themes in different years, revealing time-based clustering patterns in research focus. C Upset plot showing the overlap of research themes among the top 10 countries (ranked by H-index). Bar heights indicate the number of shared themes across different country combinations, highlighting the extent of international thematic convergence. D Venn diagram illustrating the thematic overlap among the top 5 countries (based on H-index). The intersections represent the number of shared research themes, emphasizing the collaborative or divergent thematic directions among leading contributors

Given the differences in factors such as population, economy, environmental conditions, and disease spectrum, various countries and regions present different focuses in the field of MOFs in cancer. Accordingly, the research themes of various countries or regions share certain commonalities to some extent while also exhibiting their unique emphases. Figure 6C reflects the connections and differences between the theme terms of various countries, indicating that China has more intersections with the United States (76), Iran (31), and Korea (17). This further illustrates that the field of MOFs in cancer have specific regional characteristics, and the scope of medical research gradually expands, forming a trend toward globalization. Further analysis of the cooperation between top countries indicates that China performs outstandingly in this field, with its unique research areas based on comprehensively strengthening cooperation among countries (Fig. 6D). They are assembling a research theme overlap zone with China and the United States as the central axis further demonstrates the leading positions of the two countries in this field.

Discussion

In this study, we conducted a systematic literature search of the WOSCC database for articles on metal–organic frameworks in cancer research from 2009 to 2023 through bibliometric methods and LDA topic model. The first article was published in 2009. Rowe et al. [23] first discovered that gadolinium metal–organic framework nanoparticles modified by synthesized polymers exhibit excellent imaging performance and targeting capability, which can be used to diagnose and treat cancer.

Based on the number of publications per year, the growth trend of publications in the field of MOFs in cancer research can be divided into two distinct stages. Before 2015, there was a slow growth phase, with the highest number of publications being eight in 2014. Since 2015, the application of MOFs in cancer research has shown significant growth, culminating in 460 publications by 2023, indicating a new stage of rapid development. This trend highlights the growing importance of MOFs in cancer research and suggests their substantial potential for future applications in cancer treatment. A possible reason for this development is the continuous evolution and application of nanomaterials and nanotechnology in oncology. Advances in drug discovery, regenerative medicine, diagnostics, and medical imaging have driven the increasing integration of MOFs across various aspects of cancer research. These areas include biochemical sensing, synthetic catalysis, molecular imaging, drug delivery, and cancer therapy, each demonstrating considerable potential for impactful applications [24, 25]. Specifically, in biochemical sensing, MOFs have been employed for the detection of cancer biomarkers due to their high surface area and tunable pore sizes, which facilitate effective interaction with target molecules [26]. In molecular imaging, MOFs have been investigated as contrast agents for MRI and other imaging modalities, thereby enhancing the visualization of tumor tissues [27]. In drug delivery, MOFs have shown the ability to encapsulate and release anticancer drugs in a controlled manner, thus enhancing therapeutic efficacy while minimizing adverse side effects [28]. Moreover, the application of MOFs in cancer therapy, such as photodynamic and photothermal therapies, has yielded promising results in selectively targeting cancer cells while minimizing damage to healthy tissues [29]. Additionally, increasing attention and support from various countries and research institutions have significantly contributed to the rapid growth of MOF research in recent years.

In this research field, the top 10 countries account for 96.01% of the total publications. The USA and South Korea were the first to conduct research and publish relevant literature in 2009. China has the highest number of publications, and China-centered international cooperation occupies seven positions among the top 10 countries with the highest cooperation frequency. These findings confirm China’s significant contribution and leading position in MOFs in cancer research, which may be attributed to China’s disciplinary advantages in nanomaterials and the deep integration of various scientific fields [30]. Nevertheless, despite its prominence in international collaboration, China’s MCP Ratio remains low at only 0.113, indicating that its research in this area is predominantly self-sufficient. Strengthening international collaborations and exchanges is essential to further enhancing China’s influence and leadership in this domain.

Seventeen of the leading 20 universities are situated in China, reflecting the country’s prominent position in global publication output. Despite the United States holding the second position in terms of publication volume, it has only one institution represented in the top 20. Iran, ranking third, has several universities in the top 20. In recent international collaborations, two prominent Chinese institutions, the Chinese Academy of Sciences and the Changchun Institute of Applied Chemistry, have made substantial contributions to the volume of scholarly publications. Enhancing research competitiveness through international collaboration underscores the necessity of fostering extensive partnerships among institutions, particularly in contexts characterized by limited economic or research resources.

Peer-reviewed journals are crucial for academic publishing, with core journals frequently publishing essential research in the field. Researchers can identify potential journal submissions based on the number of publications in MOFs in cancer research. Journal analysis reveals that 327 journals have published research in this field. The top ten journals have published 19.49% of the research in the field. A total of 146 (44.65%) journals have published only one paper, while 51 (15.60%) journals have published ten or more studies. ACS Applied Materials and Interfaces is the most productive journal, with 137 articles published, followed by Advanced Functional Materials (n = 53), Biomaterials (n = 41), and Advanced Materials (n = 34). Among the top 10 journals, four are from the USA, three are from Germany, two are from the Netherlands, and one is from the United Kingdom. The average impact factor (IF) of the top 10 journals was 14.76, all of which are in the JCR's first quartile (Q1). The impact factor of these journals also reflects the importance and priority of the field.

In recent years, significant progress has been made in developing MOFs for drug delivery and cancer therapy. In 2010, Horcajada et al. [19]. Synthesized a non-toxic porous iron (III)-based metal–organic framework with engineered cores and surfaces, which efficiently controlled the delivery of challenging anticancer and antiretroviral drugs such as bleomycin and doxorubicin. These iron-based MOFs also exhibited excellent imaging capabilities, making them suitable candidates for MRI contrast agents. Similarly, in 2014, Zhuang J et al. [21]. Developed nanoscale ZIF-8 spheres for drug delivery, demonstrating pH-responsive dissociation that facilitated the intracellular release of encapsulated drugs, effectively targeting cancer cells in acidic microenvironments. They also showed the multifunctionality of ZIF-8 by encapsulating iron oxide nanoparticles, imparting magnetic characteristics for enhanced imaging. In 2017, Li SY et al. [22]. Designed a cancer-targeted cascade bioreactor (mCGP) for synergistic starvation and photodynamic therapy, utilizing glucose oxidase and a photodynamic enzyme encapsulated within a porphyrin MOF. This bioreactor exhibited enhanced tumor targeting, immune escape, and retention, ultimately demonstrating a synergistic therapeutic effect by promoting intracellular oxidation and cancer starvation. Collectively, these studies highlight the versatile application of MOFs as multifunctional nanocarriers, showing substantial promise for targeted drug delivery, imaging, and synergistic cancer therapy.

While the scientific literature on MOF in cancer research is extensive, with a solid understanding of different dimensions, they tend to focus on specific issues to the neglect of the overall progress of research in this field. In this study, we represent a pioneering effort in the field to analyze keywords through the application of the LDA model. It elucidates specific topics that have emerged over the past two decades, assesses the efficacy of MOFs in cancer research, and uncovers the emergence of novel topics within the domain of tumor-related materials science [31]. Topic 1 specifically addresses nanoparticle-mediated therapies, highlighting key terms such as “therapy,” “nanoparticles,” “photodynamic,” and “tumor.” This indicates a significant interest in leveraging the hypoxic tumor microenvironment to improve the efficacy of photodynamic therapy. Topic 2 relates to the synthesis and design of drug delivery platforms, with keywords such as “synthesis,” “controlled-release,” and “nanomedicine,” reflecting ongoing efforts to develop innovative, efficient drug delivery systems, potentially revolutionizing personalized treatment approaches. Topic 3 focuses on the utilization of MOFs in cancer therapy, emphasizing key concepts such as “apoptosis,” “resistance,” and “lung cancer.” This indicates a dual emphasis on elucidating cellular mechanisms and addressing drug resistance, which holds promise for overcoming the limitations of existing therapeutic approaches. Conversely, Topic 4 examines mesoporous materials for drug delivery, with terms such as “mesoporous” and “silica” indicating a specialized and emerging field that has the potential to enhance the encapsulation and release of therapeutic agents, thereby mitigating associated side effects. Finally, Topic 5 focuses on graphene-based sensors and detection systems, highlighting the key concepts of “detection,” “graphene,” and “biosensor.” This underscores the unique properties of graphene as a promising candidate for the development of advanced biosensors, which may facilitate significant advancements in medical diagnostics, environmental monitoring, and biosecurity. Collectively, these topics delineate the diverse trajectories of contemporary research, emphasizing material innovation and its potential implications for enhancing cancer treatment and diagnostics.

The relevance analysis of MOFs in cancer research reveals three distinct stages of development, each driven by technological and scientific advancements that shaped the focus and applications of MOFs over time. The first stage, between 2009 and 2014, primarily focused on material exploration and characterization. This period was marked by significant advancements in the synthesis of MOFs, particularly in their catalytic activity, coordination polymers, and the development of copper cyanide-based materials [19, 32]. The identification of these basic properties paved the way for their potential applications in cancer research. Notably, MOFs demonstrated the ability to enhance Surface-Enhanced Raman Spectroscopy (SERS) signals through gold nanoparticle embedding, which highlighted their promise as sensitive biosensors [33]. Furthermore, their inherent porous structure and tunable chemical properties made MOFs ideal candidates for drug delivery applications, prompting early investigations into their biomedical potential. The second stage, from 2015 to 2018, saw a shift towards developing anticancer activities, with a particular focus on coordination polymers and controlled-release drug systems. During this phase, there was a growing recognition of the importance of specific MOF characteristics, such as their ability to influence biological distribution, blood circulation half-life, and targeting capabilities. A key technological advancement during this period was the increased use of post-synthetic modification (PSM), which allowed researchers to fine-tune the properties of MOFs, such as solubility, cellular uptake, and catalytic reactions [34]. These innovations significantly expanded the biological applications of MOFs, especially in drug delivery and targeting. The progress in the development of MOF-based drug carriers, as well as improved surface chemistry, set the stage for more refined applications in cancer treatment. The third and most recent stage, from 2019 to 2023, has been defined by a concerted focus on tumor treatment, encompassing photodynamic therapy (PDT), photothermal therapy, chemotherapy, and immunotherapy [35–37].This phase witnessed notable scientific advancements, including the development of light-triggered drug delivery systems using UIO-66 fibers, the design of nanoscale Hf-porphyrin MOFs for PDT with promising in vivo results, and chlorine-based MOFs for efficient PDT in colon cancer models [38].Technological progress in MOF fabrication and their functionalization has enabled the exploration of diverse therapeutic modalities, such as sono-dynamic therapy using Cu-MOFs, which enhance tumor aggregation and degradation under hypoxic conditions [39]. These innovations represent a significant leap in the clinical application of MOFs for cancer treatment, although challenges remain in areas such as controlled synthesis, surface properties, pharmacokinetics, biocompatibility, toxicity, and therapeutic efficacy.

The tumor correlation analysis performed in this study indicates that metal–organic frameworks (MOFs) are predominantly utilized in breast cancer research, followed by applications in lung, liver, colorectal, and prostate cancers. This distribution is likely due to a confluence of clinical, biological, and therapeutic factors unique to each cancer type. Numerous exemplary MOF-based nanoplatforms have been developed and documented for use in sonodynamic therapy, microwave thermal therapy, dynamic therapy, gene therapy, and gas therapy. Furthermore, the integration of multiple therapeutic strategies in combination therapy is anticipated to address the limitations associated with monotherapies, thereby facilitating more precise tumor treatment. Recently, Tian, Bian, and their colleagues developed a biodegradable “all-in-one” nanohybrid, designated as UiO-66/Au-ASO/PEG (UAAP), to enhance the radiotherapy (RT) efficacy for triple-negative breast cancer through a dual exogenous/endogenous carbonic anhydrase IX (CA IX) inhibition strategy. Gold nanoparticles (Au NPs), serving as radiosensitizers, were functionalized on the surface of UiO-66, which is composed of zirconium (Zr4 +) nodes and p-phthalic acid (PTA) ligands. Following the conjugation of thiolated CA IX antisense oligonucleotide (ASO) and polyethylene glycol (PEG) via gold-sulfur (Au–S) bonds, the biodegradable UAAP was successfully synthesized. In a related study, Li, Wen, and their team introduced a peroxidase-mimicking nanoreactor based on MIL-101, termed DHA@MIL-101, for the treatment of Lewis lung cancer using an efficient chemodynamic therapy (CDT) approach (Fig. 3D) 53. The Chinese herbal monomer dihydroartemisinin (DHA), a sesquiterpene lactone compound derived from Artemisia annua, was encapsulated within the pores of MIL-101, which is constructed from iron (Fe3 +) and 2-aminoterephthalic acid (NH2-BDC) ligands. This encapsulation resulted in DHA@MIL-101 with enhanced water solubility and biocompatibility, achieving a loading capacity efficiency of 20 weight percent (wt%) for DHA. In addition, Xinhua Zhao and coworkers explore the use of paclitaxel-coated ZIF-8 metal–organic framework nanoparticles (ZIF-8 NPs/Pacx) as a novel drug delivery system for enhanced liver cancer treatment.

Our study has several limitations. Firstly, it only includes articles written in English and recorded in the WoSCC database, which may cause deviations from reality. Since WoSCC covers the vast majority of high-quality research, this does not affect the overall trend of the results. Future studies could consider incorporating additional databases such as Scopus and PubMed for a more comprehensive review. Secondly, some results were manually standardized before analysis to reduce biases caused by different expressions of the same concept. However, with clear selection criteria, such bias can be effectively mitigated. Thirdly, we primarily relied on traditional citation metrics, such as the h-index, g-index, and m-index, to assess the impact of countries and institutions in this study. However, these citation metrics are subject to a time lag, meaning the impact of recently published high-quality studies may be underestimated. This limitation highlights the need for future research to incorporate more up-to-date impact measures, which can better capture the influence of newer publications. Furthermore, owing to the absence of objective evaluation metrics, we refrained from performing sensitivity analyses to evaluate the consistency and interpretability of thematic outcomes across varying thematic quantities within the LDA model. Despite these limitations, this study provides valuable academic insights into the developmental trends, research hotspots, and emerging frontiers of metal–organic frameworks (MOFs) within the context of cancer research.

Conclusion

This study provides a comprehensive overview of the growth and potential of MOFs in cancer research from 2009 to 2023, highlighting China’s significant contributions. MOFs exhibit considerable promise in the realms of drug delivery and cancer treatment, especially for breast, lung, and liver cancers, owing to their superior biocompatibility, stability, and versatility. Nonetheless, several critical challenges must be addressed to enable their clinical translation. Firstly, the development of scalable and cost-effective synthetic methods is crucial to ensure consistent batch production. Secondly, a deeper understanding of the pharmacokinetics and biodistribution of MOFs is essential, which can be facilitated through the application of advanced in vivo imaging and tracking techniques. Thirdly, comprehensive studies on long-term biocompatibility and toxicity are vital to confirm their safety for clinical use. Finally, proactive engagement with regulatory authorities and the establishment of standardized manufacturing protocols can expedite the market approval process. By systematically addressing these challenges, MOFs are well-positioned to make significant contributions to precision cancer therapy, providing more effective and targeted treatment options for patients worldwide.

Author contributions

All authors have participated in drafting the paper and approved the final version to be published. GL provided direction and guidance throughout the preparation of this manuscript. HYN and HPD wrote and edited the manuscript. ANH provided professional guidance on the search strategy and the rationality of this article. ZJ, XPL and WYX collected and prepared the related papers. PY reviewed and made significant revisions to the manuscript.

Funding

This work was supported by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-005A).

Data availability

The data in this study is not sensitive and is accessible in the public domain. Therefore, this dataset is readily accessible and devoid of any confidential attributes. All the data employed in this study has been integrated into the article and Supplementary Material.

Declarations

Ethics approval and consent to participate

This article does not contain any studies with human participants or animals performed by any of the authors.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.