Global research trend of graphene application in breast cancer: a bibliometric analysis

Abstract

Breast cancer (BC) is the most common malignancy among women, and its incidence has steadily increased annually. Traditional diagnostic and therapeutic approaches have limitations, prompting an urgent need to explore innovative strategies. Graphene possesses notable advantages, including strong biocompatibility, excellent biosafety, and effective active targeting, providing promising new avenues for BC treatment. This study aims to evaluate the current status and emerging trends of graphene applications in BC using bibliometric methods. Publications related to graphene and BC were retrieved from the Web of Science core collection, screened according to inclusion criteria, and analyzed using CiteSpace and VOSviewer for data analysis and visualization. A total of 1395 publications were included in this analysis. From 2010 to 2024, the number of publications increased significantly. China and Iran dominate research output in this field, with China contributing the highest number of publications, total citations, average citations per paper, and H-index. The Chinese Academy of Sciences and Duarte de Melo-Diogo are the most influential institution and author, respectively, while Biosensors and Bioelectronics are the most productive journal. Recent research hotspots include the use of graphene in photothermal therapy and biosensing for BC. This bibliometric analysis comprehensively summarizes the current application status and research hotspots of graphene in BC and identifies future application trends. These findings provide valuable insights into the utilization and development directions of graphene in BC.

Introduction

Breast cancer (BC) is the most common malignancy among women globally^[1]. Traditional diagnostic and therapeutic methods face several challenges, including limited accuracy, significant toxic side effects, and drug resistance^[2]. Due to its unique two-dimensional nanostructure, high biocompatibility, and potential for multifunctional modification, graphene offers innovative opportunities for BC diagnosis and treatment^[3]. Graphene and its derivatives can function as targeted drug carriers, enable tumor ablation through photothermal effects, or facilitate early diagnosis via highly sensitive biosensors^[4]. Additionally, they exhibit low toxicity owing to their carbon-based structure^[5].

HIGHLIGHTS

• This study puts forward the first bibliometric analysis of graphene materials in the field of diagnosis and treatment of breast cancer.

• China has made great contributions in this field. The Chinese Academy of Sciences is the most influential institution, Biosensors and Bioelectronics is the most cited periodical.

• The research trend of graphene in the field of breast cancer is gradually shifting from drug delivery to more abundant applications, such as electrochemical sensor and photothermal therapy.

• Graphene, with its unique properties and chemical structure, will overcome the limitations of existing methods and help the diagnosis and treatment of breast cancer enter a new stage.

Despite notable research progress, the field lacks comprehensive summaries and systematic reviews of the global research landscape, evolving hotspots, and interdisciplinary collaboration mechanisms. Under the premise of following the TITAN Guidelines 2025 governing declaration and use of artificial intelligence (AI)^[6], this approach addresses the qualitative limitations of traditional reviews by integrating relevant literature and utilizing bibliometric tools. It also bridges the cognitive gap between macro-level trends and micro-level technologies, providing researchers with visualized references for effective resource allocation. This study adopts a data-driven methodology to comprehensively analyze the current research state, laying the groundwork for optimizing research directions, avoiding redundant innovations, and promoting clinical translation.

Methods

Data source and search strategy

Data were obtained from the Web of Science Core Collection (WOSCC)^[7]. The search strategy was: TS = (Breast OR Mammary) AND TS = (cancer OR tumor OR carcinoma OR neoplasm OR tumorous OR neoplastic) AND TS = (graphene). The search term “graphene” retrieved all relevant literature, including graphene oxide, reduced graphene oxide, graphene quantum dots (GQDs), and graphene–gold-based nanocomposites. The search was limited to articles and reviews published in English up to November 20, 2024.

Data extraction and analysis

Information including authors, institutions, countries, journals, publication years, and citations was extracted from the final literature set for comprehensive evaluation.

VOSviewer (version 1.6.19)^[8] was employed for country, journal, keyword, and author co-occurrence analysis. Keywords were grouped into clusters based on association strength and direction, represented by distinct colors and temporal progression.

CiteSpace (version 6.3.R1)^[9] was utilized for reference burst detection, keyword burst and clustering, institution burst and co-occurrence, and author burst analysis. Parameters included a time interval of 1 year, g-index (k = 17), link retaining factor (LRF = 3.0), maximum links per node (L/N = 10), look-back years (LBY = 5), and e = 1.0. All other settings remained at default.

Results

Timeline distribution of publications

A total of 1395 publications were identified as “all records and references” (Fig. 1).

Figure 1.

Flowchart of publications screening.

Data standardization

Table 1 shows that graphene research in BC began in 2010. Between 2010 and 2024, publication numbers and citations steadily increased, peaking in 2022 (188 publications). Citations reached their highest level (8126 times) in 2017, and the highest H-index (55) occurred in 2018.

Table 1.

Timeline distribution of publications and citations

Year	TP	TC	ACPP	H-Index
2010	1	1500	1500	1
2011	6	1078	179.67	6
2012	14	1558	111.29	14
2013	22	2929	133.14	21
2014	43	2681	62.31	31
2015	54	3550	65.74	34
2016	74	4465	60.34	39
2017	119	8126	68.29	50
2018	154	7795	50.62	55
2019	121	4708	38.91	42
2020	167	5520	33.05	43
2021	178	4738	26.62	38
2022	188	3419	18.19	32
2023	157	1503	9.57	19
2024	121	148	1.11	5

Analysis of countries distribution

This study identified 73 countries, primarily including China, Iran, India, the USA, and South Korea. China had the highest number of publications (544, 39%), total citations (26 790), average citation times per paper (80.05), and H-index (101) (Table 2).

Table 2.

Top 10 countries by publication count

Country	TP	TC	ACPP	H-Index
China	544	26 790	80.05	101
Iran	283	8013	28.31	48
India	220	5861	26.64	44
USA	161	9340	58.01	49
South Korea	93	3482	37.44	32
Saudi Arabia	65	1591	24.48	21
England	37	1179	31.86	20
Turkey	37	1051	28.41	21
Egypt	36	890	24.71	15
Italy	33	998	30.24	19

The publication trends of the top five countries were further analyzed (Fig. 2). China initiated graphene research in BC first, followed by the USA and South Korea 1 year later. The publication counts for the top 10 countries demonstrated consistent fluctuations and overall growth.

Figure 2.

Publication trends of the top 10 countries.

To assess international collaboration, a cooperation network was generated (Fig. 3). Among the 73 countries, 29 (39.73%) were from Europe, 29 (39.73%) from Asia, 7 (9.59%) from Africa, 3 (4.11%) from South America, 3 (4.11%) from North America, and 3 (4.11%) from Oceania. China and India occupied central positions within the network, demonstrating extensive cooperation with other countries.

Figure 3.

Co-authorship network of countries.

Analysis of institutions distribution

This study identified the 10 most productive and influential institutions in the field of graphene applications in BC (Table 3).

Table 3.

Top 10 institutions by publication count

Institution	Country	TP	TC	ACPP	H-Index
Chinese Academy of Sciences	CHINA	65	5840	89.85	35
Tabriz University of Medical Sciences	IRAN	57	2245	39.39	29
University of Tehran	IRAN	40	1523	3.08	23
Islamic Azad University	IRAN	38	960	25.26	15
Academic Center for Education, Culture, and Research	IRAN	33	824	24.97	16
Indian Institute of Technology System, IIT System	INDIA	33	903	27.36	16
Egyptian Knowledge Bank, EKB	Egypt	32	871	27.22	15
Shanghai Jiao Tong University	CHINA	29	1218	42	17
Council of Scientific and Industrial Research, CSIR India	INDIA	28	622	22.21	14
Tehran University of Medical Sciences	IRAN	28	947	33.82	17

The Chinese Academy of Sciences had the highest productivity (65 publications), followed by Tabriz University of Medical Sciences (57 publications), and University of Tehran (40 publications). In terms of total citations, the Chinese Academy of Sciences ranked first (5840 citations), followed by Tabriz University of Medical Sciences (2245 citations). The Chinese Academy of Sciences also had the highest H-index (35). Among the top 10 institutions, 5 are from Iran, 2 from China, 2 from India, and 1 from Egypt.

Institutional collaboration was further analyzed. Figure 4a shows a collaboration network involving 298 institutions. Figure 4b illustrates the 13 institutions with the strongest citation bursts, each with a citation intensity greater than 3. The Chinese Academy of Sciences, appearing in 2010, showed the greatest citation strength (Strength = 7.6).

Figure 4.

Analysis of institutions distribution. (A) Co-authorship network of institutions. (B) Top 10 institutions with the strongest citation bursts.

Analysis of influential and co-cited journals

A total of 200 journals published articles related to graphene and BC. The top 10 journals accounted for 22.37% (312 out of 1395) of total publications (Table 4).

Table 4.

Top 10 journals by publication count

Journal	TP	TC	ACPP	H-Index	IF (2024)
Biosensors and Bioelectronics	58	4219	72.74	42	10.7
ACS Applied Materials Interfaces	48	3196	66.58	35	8.3
RSC Advances	30	777	25.9	18	3.9
Sensors and Actuators B: Chemical	30	1649	54.97	24	8
Nanomaterials	26	685	26.35	18	4.4
Journal of Drug Delivery Science and Technology	25	490	19.6	12	4.5
Microchimica Acta	25	689	27.56	16	5.3
Analytical Chemistry	24	1282	53.42	16	6.7
Journal of Materials Chemistry B	23	906	39.39	18	6.1
Scientific Reports	23	668	29.04	15	3.8

Biosensors and Bioelectronics ranked highest in total publications, total citations, average citations per publication, H-index, and impact factor (IF). The IFs of the top 10 journals were all ≥3.8.

Larger nodes in the figure indicate a greater number of publications. Lines connecting nodes represent cross-citations between journals, illustrating a positive citation relationship among journals publishing in graphene and BC (Fig. 5a). Purple indicates that entered the field earlier, while yellow indicates newly emerged journals in the current year (Fig. 5b).

Figure 5.

Citation network of journals.

Analysis of highly cited articles

Table 5 presents the 10 most cited articles in graphene and BC research. Four articles were cited more than 500 times. The most cited article (1501 citations) was titled “Functional Graphene Oxide as a Nanocarrier for Controlled Loading and Targeted Delivery of Mixed Anticancer Drugs,” published by Zhang LM in Small (2010).

Table 5.

Top 10 most cited articles

Year	First author	Title	Journal	Citations
2010	Zhang, LM[10]	Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs	Small	1501
2017	Tao, W[11]	Black phosphorus nanosheets as a robust delivery platform for cancer theranostics	Advanced Materials	733
2016	Ou, LL[12]	Toxicity of graphene-family nanoparticles: a general review of the origins and mechanisms	Particle and Fibre Toxicology	534
2013	Wang, YC[13]	Comparison study of gold nanohexapods, nanorods, and nanocages for photothermal cancer treatment	ACS Nano	530
2013	Yoon, HJ[14]	Sensitive capture of circulating tumor cells by functionalized graphene oxide nanosheets	Nature Nanotechnology	462
2015	Chen, Q[15]	An imagable and photothermal “abraxane-like” nanodrug for combination cancer therapy to treat subcutaneous and metastatic breast tumors	Advanced Materials	400
2021	Gaves, S[16]	Nanoparticles for cancer therapy: current progress and challenges	Nanoscale Research Letters	389
2017	Zang, AG[17]	Tunable photoluminescence of water-soluble AgInZnS-graphene oxide (GO) nanocomposites and their application in-vivo bioimaging	Sensors and Actuators B: Chemical	365
2017	Yao, XX[18]	Graphene quantum dots-capped magnetic mesoporous silica nanoparticles as a multifunctional platform for controlled drug delivery, magnetic hyperthermia, and photothermal therapy	Small	350
2012	Cheng, L[19]	Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy	Biomaterials	321

Analysis of keywords co-occurrence and hotspots

A total of 6359 keywords were identified in this dataset. Supplemental Digital Content Table S1 lists the 20 most frequent keywords. “Breast cancer,” “graphene oxide,” “nanoparticles,” “drug delivery,” and “graphene” were the five most frequent keywords (Fig. 6), indicating significant attention in this field.

Figure 6.

Keyword co-occurrence and hotspot analysis. (A–B) Keyword co-occurrence network. (C) Top 20 keywords with the strongest citation bursts. (D) Visualization and clustering network of keywords.

The keyword co-occurrence network was established using all keywords, divided into six major clusters (Fig. 6a). Cluster 1 (red) primarily concerned the application of gold nanoparticles in BC. Cluster 2 (green) addressed graphene oxide-based drug delivery in vivo and photothermal therapy (PTT) applications. Cluster 3 (yellow) focused on “nanoparticles” and “graphene quantum dots.” Cluster 4 (dark blue) dealt mainly with topics related to reduced graphene oxide. Cluster 5 (purple) emphasized drug delivery applications of graphene materials, while Cluster 6 (light blue) concentrated on carbon nanotubes. “Graphene oxide,” “controlled-release,” “biosensor,” and “cytotoxicity” have become recent research hotspots (Fig. 6b).

The study further analyzed the top 18 keywords with the strongest citation bursts over 25 years (Fig. 6c). The earliest burst keyword was “graphite oxide” (2010, strength = 3.9). All keyword burst strengths were above 2.89, with five keywords above 5. “In vitro” showed the strongest citation burst (strength = 7.88), emerging in 2014 and subsiding by 2017. Changes in keyword citation bursts reflect shifts in the research emphasis regarding graphene applications in BC. “Nano graphene” and “amplification” became hotspots from 2017, whereas “adsorption” and “antibacterial activity” emerged since 2020.

Figure 6d illustrates six clusters of varying colors and sizes, representing distinct research themes from the past 15 years: #0 “biosensor,” #1 “photothermal therapy,” #2 “targeted delivery,” #3 “oxidative stress,” #4 “cancer cells,” and #5 “electrochemical sensor.” Clusters “#1 photothermal therapy” and “#5 electrochemical sensor” are relatively larger.

Keyword co-occurrence analysis revealed a research shift in graphene applications for BC, transitioning from traditional drug delivery to advanced diagnostics and therapies. Initially, research emphasized “drug delivery” and “nanoparticles,” highlighting graphene’s fundamental carrier properties. After 2010, interest surged in “photothermal therapy.” Following verification of its near-infrared (NIR) absorption capabilities, graphene was combined with “targeted delivery,” creating multifunctional therapeutic systems. Since 2013, “biosensors” and “electrochemical sensors” have gained prominence. Technological advances now enable precise detection of exosomes and circulating tumor miRNAs, enhancing early diagnosis. Recently emerging keywords, such as “multimodal therapy” and “nanographene amplification,” indicate a research evolution toward intelligent diagnostic and therapeutic platforms, aligning with innovative precision medicine demands.

Analysis of co-cited authors

Figure 7 presents the author’s collaboration network diagram. A total of 279 authors participated in research related to graphene applications in BC. Among them, Duarte de Melo-Diogo was the most influential author, publishing 16 papers. Wei Qin had the highest total citations (730 times) and highest average citations per paper (66.36). Hassan Namazi achieved the highest H-index (12) (Table 6).

Figure 7.

Analysis of co-cited authors. (A–B) Co-occurrence network of authors. (C) Top 4 authors with the strongest citation bursts.

Table 6.

Top 10 authors by publication count

Authors	TP	TC	ACPP	H-index
de Melo-Diogo, Duarte	16	440	27.5	11
Namazi, Hassan	14	501	35.79	12
Correia, L. J.	14	436	31.14	11
Naghib, Seyed Morteza	14	488	34.86	9
Lima-Sousa, Rita	14	408	29.14	10
Rhee, Kyong Yop	13	12	14	6
Zare, Yasser	13	182	14	6
Alves, Cátia	13	404	31.08	10
Hasanzadeh, Mohammad	12	571	47.58	11
Wei, Qin	11	730	66.36	11

Figure 7c shows the citation activity of the top four authors. He Li had the longest citation burst duration (2013–2017), indicating his significant contribution to graphene applications in BC. Citation bursts for Yasser Zare, Kyong Yop Rhee, and Ana M. Diez-Pascual have been active since 2022, highlighting their innovative contributions to this field. Table 6 summarizes the TP, TC, ACPP, and H-index for the 10 authors with the highest total publications.

Duarte de Melo-Diogo emerged as a leading researcher in nano-mediated combination cancer therapy, utilizing a three-fold approach: material design, model innovation, and mechanism elucidation. His research concentrates on designing nanocarriers, developing tumor microenvironment-responsive delivery systems, and evaluating 3D models. His primary focus is on the synergistic combination of photothermal and photodynamic therapies (PTT/PDT) with chemotherapy and gene therapy. His contributions extend beyond creating highly effective, low-toxicity nanocarriers to establishing standardized 3D evaluation systems, advancing the field from material preparation toward clinical relevance. With ongoing research in injectable hydrogels and immune-combination strategies, his work significantly influences the translational trajectory of cancer therapy.

Wei Qin developed distinct expertise in biomedical nanomaterials through three core technologies: environmentally responsive material design, multimodal signal amplification, and tumor microenvironment analysis. His research addresses key challenges in targeting, sensitivity, and safety of nanocarriers. Furthermore, his work accelerates the transition of nanomaterials from laboratory research to practical application through validation in 3D tumor models and preclinical translational studies. Qin’s integrative “materials – devices – therapeutic efficacy” approach offers nanomaterial-based solutions for critical medical issues, including cancer treatment and early diagnosis.

Since 2022, authors such as Yasser Zare and Kyong Yop Rhee have notably contributed to research focusing on “electrochemical sensors-exosome detection.” Keywords such as “amplification” and “circulating tumor miRNAs” appear frequently in highly cited recent literature. Meanwhile, Ana M. Diez-Pascual focuses her research on elucidating the antitumor mechanisms of graphene-based composites.

Analysis of co-cited references

Over the past 15 years, a total of 248 studies on graphene applications in BC have been co-cited. The most frequently cited reference, “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries,” was published by Sung et al in CA: A Cancer Journal for Clinicians in 2021. The reference with the highest centrality (0.53) was “Development of a Graphene Oxide Nanocarrier for Dual-Drug Chemo-phototherapy to Overcome Drug Resistance in Cancer,” published in ACS Applied Materials & Interfaces in 2015. Table 7 provides detailed information on the top 10 cited references. Each reference was cited at least 16 times.

Table 7.

Top 10 co-cited references

Title	First author	Year	Journal	TC	Co-citation	Centrality
Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[1]	Sung H	2021	CA-A Cancer Journal for Clinicians	46 748	29	0.08
Nano-graphene in biomedicine: theranostic applications[20]	Yang K	2013	Chemical Society Reviews	1372	26	0.15
An electrochemical nanobiosensor for plasma miRNA-155, based on graphene oxide and gold nanorod, for early detection of BC[21]	Azimzadeh M	2016	Biosens Bioelectron	274	26	0.18
Graphene in mice: ultrahigh in vivo tumor uptake and efficient photothermal therapy[22]	Yang K	2010	Nano Letters	2096	25	0.05
Functional graphene oxide as a nanocarrier for controlled loading and targeted delivery of mixed anticancer drugs[10]	Zhang LM	2010	Small	1501	23	0.04
Ultrasmall reduced graphene oxide with high near-infrared absorbance for photothermal therapy[23]	Robinson JT	2011	Journal of The American Chemical Society	1848	17	0.13
In vivo targeting of metastatic BC via tumor vasculature-specific nano-graphene oxide[24]	Yang DZ	2016	Biomaterials	99	16	0.16
The chemistry of graphene oxide[25]	Dreyer DR	2010	Chemical Society Reviews	9547	16	0.2
Graphene and graphene oxide as new nanocarriers for drug delivery applications[26]	Liu JQ	2013	Acta Biomaterialia	1048	16	0.07
In vitro toxicity evaluation of graphene oxide on A549 cells[27]	Chang YL	2011	Toxicology Letters	1097	16	0.28

Figure 8b illustrates the top 15 references with the strongest citation bursts, which began appearing as early as 2008. All these references had burst intensities greater than 3, with 11 references exceeding a strength of 5, and 2 references surpassing a strength of 10. The strongest citation burst (Strength = 12.54) occurred for a reference published in 2015.

Figure 8.

Analysis of co-cited references. (A) Co-citation network map. (B) Top 20 references with the strongest citation bursts.

Graphene research in BC exhibits a “bench-to-bedside” trajectory. Zhang et al^[10] pioneered the development of a graphene oxide-based targeted drug delivery system, establishing an active targeting paradigm. Robinson et al^[23] addressed efficiency and toxicity issues in PTT by creating ultra-small reduced graphene oxide. Yang et al^[20] systematically summarized interdisciplinary applications in their comprehensive “theranostics” review, while Dreyer et al^[25] provided essential chemical insights into graphene oxide, supporting toxicity evaluations and material modifications. These seminal publications form the core of co-citation networks, directly influencing research hotspots such as “photothermal therapy” and “biosensing,” thus laying theoretical and technical foundations for clinical translation.

Discussion

To our knowledge, this is the first comprehensive bibliometric analysis of graphene application research in BC. Findings indicate a generally upward trend in publication numbers. An increasing number of countries, institutions, and researchers have become involved in this area, accelerating its rapid advancement.

BC remains a leading cause of death among women globally. Although substantial progress has been made in BC diagnosis and treatment, managing drug resistance, advanced disease stages, and adverse treatment events remains challenging. There is an ongoing need to develop targeted and specific drug-delivery systems to enhance therapeutic efficiency and minimize toxicity from nonspecific drug distribution^[28]. Graphene exhibits inherent anticancer properties, enhancing cell adhesion and capturing BC cells^[29]. Studies indicate graphene’s potential cytotoxic effects on tumor cells through oxidative stress and autophagy^[30]. Additionally, graphene reduces macrophage activity, induces oxidative damage, inhibits BC cell migration and invasion, and suppresses tumor growth and metastasis^[31]. Previous research demonstrates that graphene exhibits relatively low toxicity to normal cells at conventional concentrations. Modified graphene displays enhanced active targeting, accumulates effectively at tumor sites, and is gradually cleared from the body, highlighting excellent biocompatibility and biosafety^[32].

The application of graphene in PTT for BC

Currently, conventional BC treatments still have limitations, including adverse side effects, multidrug resistance, and cancer recurrence^[33]. To overcome these drawbacks, PTT based on light irradiation has been introduced to control BC effectively. This method is noninvasive, low-toxicity, highly efficient, and controllable^[34]. The mechanism of PTT involves destroying cancer cells by generating heat or reactive oxygen species (ROS) after irradiating lesions, particularly with NIR light^[35]. PTT induces cellular stress, activates autophagy-related genes, and initiates autophagy to influence the survival, differentiation, or death of cancer cells^[36].

However, PTT in BC faces challenges, including the limited penetration depth of NIR irradiation and low photothermal conversion efficiency, resulting in incomplete tumor ablation and higher recurrence risk^[37]. To address these limitations, photosensitizers must exhibit high NIR-region absorption and selective uptake by BC cells, enabling precise heating of tumor cells^[38]. Graphene’s excellent NIR absorption and surface activity give it considerable potential as a photothermal therapeutic agent for BC^[39]. Incorporating targeting agents into graphene enhances its specificity, improving the ablation effect of PTT^[40]. Additionally, graphene-based multifunctional hybrid nanomaterials exhibit stronger photothermal effects^[41]. Typically, high-power NIR irradiation is used to achieve deeper penetration but risks damaging surrounding normal tissues, especially during prolonged irradiation. Nevertheless, graphene-based nanocomposites effectively kill BC cells even under low-intensity lasers^[42].

The HPAA/GO-RGD@DOX system designed by Zhu et al^[43] utilizes GO as a carrier, surface-modified with poly(β-amino ester) and grafted with RGD peptides for doxorubicin (DOX) loading. Employing pH-responsive chemical bonds, this system releases drugs in the acidic tumor microenvironment and achieves combined photothermal-chemotherapy via NIR laser irradiation^[43]. Zhou et al^[44] utilized 3D printing technology to produce polyurethane scaffolds functionalized with graphene nanosheets. Leveraging 4D printing properties, these scaffolds act as stimulus-responsive tissue expanders in vivo and as photothermal ablation agents under laser irradiation.

Chen et al^[45] developed a hierarchical drug delivery system using rGO nanosheets as photosensitizers. Through surface modification, the system co-delivers anti-PD-L1 antibodies and exosome inhibitors. Combined with PTT, it activates systemic antitumor immunity and remodels the tumor immune microenvironment^[45]. Itoo et al^[46] synthesized GO(OX)PB(1/1/0.2)NPs nanocomposites by conjugating polyethylene glycol (PEG)-modified graphene oxide with oxaliplatin prodrugs and PEGylated biotin. Precise ratio optimization ensures targeted delivery via biotin binding, enabling synergistic chemotherapy and photothermal therapy^[46].

All four research teams introduced innovative BC treatment methods through novel material designs and combined strategies. These methodologies integrate material preparation, performance optimization, and therapeutic design. Both in vitro and in vivo experiments demonstrated significant tumor suppression, providing new effective pathways and potential solutions for BC therapy.

The application of graphene as a biosensor in BC

BC remains one of the leading causes of cancer-related death among women^[47]. Early BC detection facilitates timely treatment, reduces mortality, and improves patient survival rates. Current detection methods include imaging, genetic screening, and tumor marker detection^[48]. However, imaging techniques lack sufficient sensitivity and specificity for accurate detection of small early-stage lesions and do not enable real-time tumor imaging, failing to meet clinical requirements for early diagnosis^[49]. Additionally, these methods are time-consuming, expensive, and can yield false-positive or false-negative results^[50]. They may also lead to complications or even cause cancer or other diseases^[51]. With the ongoing advancement of nanotechnology, graphene-based biosensors have attracted considerable attention. They offer advantages such as high sensitivity and specificity, rapid analysis, label-free detection, low cost, excellent biocompatibility, miniaturization, and integration of diagnostic and therapeutic functions, presenting promising opportunities for early BC detection^[52]. Recently, biosensors have garnered attention for early BC diagnosis due to their superior sensitivity, simplicity, low cost, and low detection limits compared to conventional methods^[53].

Khodaie et al^[54] constructed a surface plasmon resonance sensor integrating graphene with MXene to detect carcinoembryonic antigen. Sun et al^[55] developed a flexible biosensor based on field-effect transistors, demonstrating potential for wearable devices capable of detecting miRNA in sweat. Yu et al^[56] designed an endonuclease-triggered detection platform combining oligonucleotide probes with graphene oxide to quantitatively measure miR-1246, exhibiting significantly enhanced sensitivity over enzyme-free systems and effectively distinguishing patients from healthy controls in clinical trials. García-Fernández et al^[57] developed an electrochemiluminescent DNA biosensor incorporating graphene nanosheets, capable of identifying single mutations in the BRCA1 gene with extremely low detection limits, validated through real sample analysis. Guo et al^[58] created an electrochemiluminescent cell sensor using PtCo@rGO nanozymes and Au@CNTs bioconjugates, enabling broad linear-range detection of circulating tumor cells in BC, with single-cell-level sensitivity. Parihar et al^[59] fabricated a cerium oxide-graphene oxide nanocomposite aptasensor for noninvasive EGFR detection via electrochemical impedance spectroscopy, suitable for real-time clinical monitoring.

All six studies employed graphene or its derivatives as core materials, functionalized by composite formation or biomolecular conjugation. Utilizing diverse optical and electrical detection methods, these systems achieved ultrasensitive detection of BC-related biomarkers. Results consistently demonstrated extremely low detection limits, surpassing traditional methods. Both ex vivo experiments and clinical validations effectively distinguished BC patients from healthy individuals, highlighting advantages such as noninvasive or minimally invasive detection. Collectively, these studies provide innovative technological solutions and direction for early diagnosis, real-time monitoring, and personalized medicine in BC management.

Contribution to existing literature

This study contributes significantly to the existing literature by providing the first systematic and quantitative bibliometric analysis specifically examining graphene applications in breast cancer. Unlike prior qualitative reviews, our approach identifies key institutions, authors, journals, and trends through objective bibliometric tools. This enhances understanding of global research dynamics and highlights shifts in research hotspots toward precision medicine, photothermal therapy, and advanced biosensing.

Future applications of graphene in BC

How can graphene-based nanomedicine contribute to precision medicine in BC treatment?

In precision therapy for BC, the multifunctional properties of graphene significantly contribute through interdisciplinary innovation. Its two-dimensional planar structure and modifiable surface allow efficient targeted drug delivery. Functionalized GO loaded with dual drugs enables pH-responsive release in the acidic tumor microenvironment^[10]. Graphene’s photothermal conversion property, combined with chemotherapy, produces a synergistic effect, facilitating simultaneous thermal ablation and drug release under NIR irradiation^[60]. A hybrid graphene oxide-GQD system improves chemotherapeutic drug delivery efficiency through photothermal disruption of cancer cell membranes^[61]. The fluorescence imaging capability of GQDs promotes theranostic platform development, while GO-functionalized surface-enhanced Raman scattering (SERS) immunosensors enable picogram-level detection of BC biomarkers^[62]. Magnetic GO nanoparticles combined with MRI-guided PTT permit real-time monitoring of nanoparticle distribution and temperature^[63]. Surface modifications such as chitosan coating and phosphoramidate functionalization substantially enhance graphene’s biocompatibility, reducing hematotoxicity and ROS generation^[64]. Both in vitro and in vivo studies confirmed its biosafety^[65]. These integrated properties – encompassing material science-based carrier design, oncology-based target analysis, and biomedical engineering-driven technological translation – provide comprehensive solutions for precision medicine in BC, including targeted delivery, synergistic therapy, real-time monitoring, and safety optimization.

Challenges in clinical translation of graphene

Graphene shows promising potential in BC therapy due to its unique physicochemical properties. However, clinical translation faces several obstacles, including toxicity risks, complex regulatory processes, and challenges in large-scale production. Addressing these requires interdisciplinary research and technological innovation. Graphene’s nanoscale dimensions and surface properties may induce biotoxicity, such as oxidative stress and cellular damage. Nevertheless, surface functionalization significantly enhances biocompatibility. Increasing research focuses on reducing hemotoxicity using polymer coatings^[66]. Experimental and theoretical studies of phosphoramide-functionalized GO demonstrate that specific functional group modifications can modulate material-biointerface interactions, decreasing nonspecific adsorption and toxicity^[64].

The interdisciplinary nature of graphene-based nanomedicine complicates regulatory pathways. Regulatory agencies, such as the U.S. Food and Drug Administration, currently require comprehensive data on material characterization, pharmacokinetics, and toxicology for nanomedicine approval. However, standardized detection methods for critical parameters, including graphene size distribution and charge state, remain lacking. For instance, batch-to-batch variations in GO-functionalized SERS immunoassay platforms, used for parallel analysis of BC cells and proteins, may impact diagnostic accuracy^[62]. Additionally, the complex mechanisms underlying multifunctional graphene nanosystems integrating imaging and therapeutic capabilities are incompatible with traditional evaluation models designed for single-target drugs^[65].

Industrial-scale graphene production is limited by low yield, insufficient purity, and complex manufacturing processes. While chemical vapor deposition can produce high-quality graphene, the high equipment cost and energy consumption hinder its pharmaceutical-grade application. Although redox methods are more economical, they often introduce oxygen-containing groups and metal impurities, compromising material uniformity^[10]. Emerging techniques like ultrasound-assisted liquid-phase exfoliation improve graphene dispersibility and yield, but solvent recovery and environmental concerns in large-scale production remain unresolved.

Despite these challenges, graphene-based nanomaterials hold considerable promise for BC therapy. Establishing standardized frameworks for systematic toxicity assessment and dose-effect relationship characterization, fostering collaboration between academia and regulatory agencies to develop standardized guidelines for structural characterization, quality control, and efficacy evaluation, and advancing cost-effective, scalable, and environmentally friendly synthesis methods could accelerate graphene’s translation from laboratory research into clinical practice.

Interdisciplinary collaboration among materials science, oncology, and biomedical engineering

In BC diagnosis and treatment, interdisciplinary collaboration among materials science, oncology, and biomedical engineering has established an innovative research paradigm. Materials science addresses precise drug delivery by designing functionalized graphene-based targeted carriers^[66]. These carriers undergo surface modification with targeting peptides or responsive groups, directly anchoring to specific targets identified by oncology research^[62]. Oncology provides pathological mechanisms guiding material design. For example, based on EMT pathway dysregulation, PEG-GO@XN nanocomposites were developed to inhibit BC metastasis, with efficacy and safety validated through 3D tumor spheroid models and animal orthotopic transplantation experiments^[67]. Biomedical engineering acts as a translational bridge, integrating graphene’s photothermal and fluorescence imaging capabilities into a theranostic platform. This platform enables real-time MRI monitoring of drug distribution and therapeutic response, while establishing standardized multiscale evaluation systems^[63]. This collaborative framework of “material design–mechanism validation–technology implementation” not only addresses therapeutic bottlenecks arising from BC heterogeneity but also advances graphene-based nanomedicine toward personalized precision medicine.

Conclusion

Current BC diagnosis and treatment face multiple challenges, including insufficiently specific biomarkers, large sample size requirements, and lengthy clinical testing. Although graphene-based biosensors offer advantages such as high sensitivity and wide dynamic detection ranges, bottlenecks in large-scale production, stability, and biocompatibility must be overcome.

Future research should focus on three directions: (1) developing graphene-based multimarker detection platforms integrating HER2-ECD, circulating tumor miRNA, and exosome detection, coupled with AI algorithms to create intelligent diagnostic models and address insufficient precision from single biomarkers; (2) optimizing biocompatibility via atomic-layer deposition and biomimetic modifications to achieve tumor microenvironment-specific drug release linked with photothermal effects, balancing anticancer efficacy and toxicity; (3) establishing collaborative networks of “material scientists-clinical pathologists-AI engineers” to validate graphene sensors’ clinical applicability using 3D-bioprinted tumor models, while advancing green synthesis technologies and standardized production methods to accelerate clinical translation. Additionally, graphene’s potential in gene-editing vectors, multidrug-resistance reversal, and combined immunotherapy warrants further interdisciplinary exploration. Only through breakthroughs in collaborative innovation in “detection accuracy-material toxicity-production standardization” can graphene transition from “proof of concept” to clinical implementation, reshaping precision BC diagnosis and treatment.

Graphene applications in BC have advanced from “material exploration” to the critical stage of “precision diagnosis and treatment.” The global knowledge graph constructed in this study systematically summarizes the past 15 years of research and serves as a “navigation map” for future developments. By quantitatively analyzing technical bottlenecks and cutting-edge directions, it provides an actionable roadmap for graphene’s translation from laboratory research to clinical practice, driving BC management toward “efficiency, minimally invasive procedures, and personalization.”

In summary, our bibliometric analysis clearly identifies the field’s unique contributions and future challenges, offering valuable insights and practical guidance for researchers pursuing clinical translation of graphene-based technologies in BC.

Strengths and limitations

This study has several unique strengths. First, it systematically analyzed graphene research in BC using bibliometric methods for the first time, providing comprehensive guidance for researchers. Second, two widely used bibliometric tools were employed simultaneously, likely ensuring objectivity in data analysis. Lastly, compared with traditional reviews, bibliometric analysis offers a more comprehensive understanding of research hotspots and frontiers.

However, this study also has limitations. First, the analysis was based solely on the WoSCC database, potentially omitting relevant studies from other sources. Second, studies were limited to English-language publications, underrepresenting non-English literature. Lastly, the 2024 dataset was incomplete, covering only publications until November 20.

Ethical approval

Given that the data originated from the publicly accessible WoSCC database, obtaining ethical approval from an institutional review board was deemed unnecessary.

Consent

Ethical approval and patient consent were not required for the analyses conducted, as they were solely based on literature research.

Sources of funding

This work was supported by the National Natural Science Foundation of China (No.82374452) to Jingwei Li.

Author contributions

Conceptualization: M.Z. and J.L.; data collection, analysis and data standardization: M.Z., D.P., and M.Y.; original draft preparation: M.Z.; review and editing: G.S. and J.L.; visualization: M.Z. and D.P. All authors contributed to the article and approved the submitted version.

Conflicts of interest disclosure

The authors declare no potential conflicts of interest with respect to this research, including any commercial or financial relationships.

Research registration unique identifying number (UIN)

It is not necessary for this research to have Research Registration Unique Identifying Number (UIN).

Guarantor

Jingwei Li.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

The data sets generated and analyzed during the study are publicly available. Access to the data can be provided through the Web of Science Core Collection. All data used in this study are included within the manuscript or available as Supplemental Digital Content.