The increase or decline in publications over time can reveal research interest in specific fields, providing quantitative insights for subject research and publication. In this study, a total of 4108 publications related to hydrogels in oncology drug delivery were retrieved, including 3110 research articles and 998 review articles, with 15,496 participating authors and 3293 participating institutions, published in 664 journals in 98 scientific categories.

Annual research output is shown in Figure 3A . Five papers related to hydrogels in oncology drug delivery were published in 2000, and two in 2001. Publication numbers remained low from 2000 to 2007, followed by a rapid increase from 2008 to 2015. The growth rate further accelerated after 2016, peaking in 2024. The International Journal of Biological Macromolecules was the most prolific journal (n=193 publications), followed by the Journal of Drug Delivery Science and Technology (n=101) and the Journal of Controlled Release (n=98). Figure 3B and Table 1 list the top 20 most productive journals, providing a useful reference for researchers considering manuscript submissions.

A co-citation network was generated ( Figure 4 ) to illustrate the relationships between publications in the field of hydrogels for oncology drug delivery from 2000 to 2024. The network comprised 1652 nodes and 6764 links, indicating extensive interconnections within this research area. Early literature (2000-2010), represented by densely interconnected gray nodes, forms the foundational “roots”, supporting the field’s subsequent growth. During the mid-period (2011-2017), blue-marked nodes became more dispersed, forming the main research branches. In the later period (2018-2024), nodes develop into tighter clusters, indicating concentration and differentiation within the field. Key publications driving this research, with their respective co-citation frequencies, included Sung H (2021) (16) (n=120), Ding SY (2016) (17) (n=116), Sun ZY (2020) (18) (n=99), Chen Q (2019) (19) (n=79), Norouzi M (2016) (20) (n=68), Wang C (2018) (21) (n=64), Senapati S (2018) (22) (n=61), Narayanaswamy R (2019) (23) (n=57), Mitchell MJ (2021) (24) (n=55), and Chao Y (2020) (25) (n=54). This concentration and differentiation of research clusters were further clarified in subsequent reference timeline plots. Citation histories of these research articles, visualized using HisCite Pro 2.1, are summarized in Table 2 . The top three cited papers were “Injectable hydrogel-based drug delivery systems for local cancer therapy” (20), “Local drug delivery strategies for cancer treatment: Gels, nanoparticles, polymeric films, rods, and wafers” (26), and “Hydrogel-based controlled drug delivery for cancer treatment: A Review” (18). Larger nodes in the graph indicate greater citation frequency and, thus, greater importance of the referenced work.

Figure 5 presents the scientific cooperation networks for countries, institutions, and authors, generated using CiteSpace and VOSviewer. The national collaboration network ( Figure 5A ) comprised 98 nodes and 788 links, with node size reflecting the volume of publications, ranging from China (largest) to the United States, India, Iran, and South Korea. The institutional collaboration network ( Figure 5B ) consists of 534 nodes and 660 links, with the Chinese Academy of Sciences, Sichuan University, the Indian Institutes of Technology System (IIT System), and Tabriz University of Medical Sciences representing prominent nodes. The author collaboration network is shown in Figure 5C . Pourmadadi Mehrab, Rahdar Abbas, Qian Zhiyong, and Abdouss Majid exhibited the highest publication counts in this field. The dense interconnections among these authors signify substantial collaborative activity ( Supplementary Table S1 in the Supplementary Materials ). Notably, a clustering effect was observed among the nodes representing Pourmadadi Mehrab, Rahdar Abbas, and Pandey Sadanand, indicating a close collaborative group. Similarly, Qian Zhiyong, Zhang Yu, and their co-authors formed another distinct cluster.

Of the 98 relevant categories, 94 experienced citation bursts between 2000 and 2024. Blue lines indicate the time interval, while red portions highlight the burst timeframe. Figure 6 presents the top 50 categories with the highest burst intensity over time. The “Engineering, Biomedical” category exhibited a burst between 2007 and 2010, with a peak intensity of 6.8. Notably, the subject category bursts have diversified over time, as seen with “Chemistry, Physical” (2009-2011), “Physics, Applied” (2012-2013), “Nuclear Science & Technology” (2014-2018), “Physics, Multidisciplinary” (2018-2020), and “Computer Science, Artificial Intelligence” (2022-2024). This shift in emergent categories reflects the multidisciplinary nature of the field. In addition, 20 emergent categories originated in 2020 or later ( Supplementary Table S2 in the Supplementary Materials ). The top three, based on recent burst activity, are “Chemistry, Applied” (2023-2024), “Engineering, Environmental” (2021-2024), and “Biochemistry & Molecular Biology” (2023-2024).

A more detailed analysis of active hydrogel content within oncology drug delivery was conducted by examining keyword burst patterns from 2000 to 2024. Of the 759 keywords that exhibited bursts at various times, the top 50 with the highest burst intensity are presented in Figure 7 . “Copolymers” showed the highest burst intensity (12.29) between 2002 and 2016, followed by “block copolymers” (10.82) between 2004 and 2015, and “n-isopropylacrylamide” (9.07) between 2002 and 2014. Notably, 20 keywords remained active in 2024, suggesting potential future research hotspots. Examples include “immunotherapy” (11.07, 2023-2024), “immunogenic cell death” (7.69, 2022-2024), “carboxymethyl cellulose” (6.46, 2022-2024), and “antibacterial” (6.46, 2022-2024). The burst intensity for “antibacterial” specifically between 2021 and 2024 was 6.42 ( Supplementary Table S2 , Supplementary Materials ).

A total of 1,534 references were identified as having burst citations. The 30 most frequently cited references between 2000 and 2024 are shown in Table 3 . Li JY (2016) (17) exhibited the highest citation burst rate, spanning from 2019 to 2021. The article concluded that hydrogel drug delivery systems provide beneficial therapeutic effects and have been used in clinical settings. Mura S (2013) (27) experienced a citation burst from 2015 to 2018, noting the recent surge in interest in advanced nanoscale drug delivery systems, particularly within nanomedicine. Norouzi M (2016) (20) had the third highest citation burst rate, attracting considerable attention upon publication and continuing for four years, from 2017 to 2021.

From 2004 onwards, 187 references exhibited citation bursts, with the top 20 strongest bursts detailed in Table 4 . Of these, six were review articles and 14 were original research articles. Notably, all these publications experienced citation bursts either in the year of publication or the following year. The review articles provide valuable guidance for research on hydrogels in oncology drug delivery, while the research articles serve as excellent references for applications of hydrogels in this field. This observation highlights the importance of researchers in the field of hydrogels for oncology drug delivery paying close attention to this rapidly evolving body of literature.

There exists a close relationship between different keywords. These keywords can generate different clusters, and the identification of these clusters can indicate various subfields of hydrogel in cancer drug delivery research. The past 24 years were divided into four six-year phases, with keyword clustering snapshots for each phase shown in Figure 8 . The first clustering (2000-2006), based on 54 papers, yielded 9 clusters, including #0 cancer therapy, #1 polyethylene glycol (PEG), and #2 localization ( Figure 8A ). The second clustering (2007-2012), analyzing 298 papers, produced 11 clusters, including #0 systems, #1 nanocomposites, and #2 DNA ( Figure 8B ). The third clustering (2013-2018), encompassing 1105 papers, generated 9 clusters, such as #0 drug delivery, #1 thermosensitive hydrogel, #2cross linking, and 9 other clusters ( Figure 8C ). The fourth clustering (2019-2024), including 2651 papers, resulted in 8 clusters, including #0 tissue engineering, #1 immunogenic cell death, and #2 nanocomposite hydrogel ( Figure 8D ). While classical areas like cancer therapy and drug delivery remain active research areas, emerging clusters such as #0 tissue engineering, #1 immunogenic cell death, #2 nanocomposite hydrogel, #3 skin cancer, #5 cancer immunotherapy, #6 graphene quantum dots, and #7 glioblastoma have gained increasing attention compared to the previous 15 years.

Analysis of emerging literature clusters revealed a focus on key areas within hydrogel research for oncology drug delivery. Cluster 0#, “tissue engineering,” comprises 77 articles. Cluster 1#, “immunogenic cell death,” and Cluster 5#, “cancer immunotherapy,” contain 76 and 58 articles, respectively, reflecting research into various cell death mechanisms and the role of hydrogels in tumor immunotherapy. Cluster 2#, “nanocomposite hydrogel,” and Cluster 6#, “graphene quantum dots,” with 71 and 56 articles, respectively, explore different nanomaterials for tumor drug delivery. Cluster 3#, “skin cancer,” and Cluster 7#, “glioblastoma,” with 61 and 47 articles, respectively, examine the application of hydrogels in treating specific tumor types. Supplementary Table S3 ( Supplementary Materials ) provides detailed data for the fourth clustering period (2018-2024), including “representative keywords within the clusters” that identify core research areas within the most recent phase of hydrogel research for oncology drug delivery.”

As shown in Figure 9 , linked keywords form specific research modules, and keywords form new modules over time. Over the past 25 years, some high-traffic keywords have persisted, some have increased in importance and popularity, while others have disappeared. Supplementary Table S4 ( Supplementary Materials ) lists the top five highest-traffic module keywords for each year. Notably, the keywords within Module 1 in 2024 diverged or converged at this research turning point, forming the largest research tributary (highlighted in red). This suggests that Module 1 represents the most enduring research module. Figure 2 maps all keywords for the top six modules in 2024. Module 1, designated “peritoneal_carcinomatosis”, encompasses 21 keywords, such as tumor growth, therapeutic efficacy, and esophageal cancer ( Figure 2A ). Module 2, named “iron_oxide_nanoparticles”, contains 13 keywords, such as DNA, ferroptosis, efficiency, and antibody ( Figure 2B ). Module 3, “drug_delivery”, comprises 16 keywords such as nanoparticles, release, in vitro, and pH ( Figure 2C ). Module 4, “release_kinetics”, contains 8 keywords, such as cytotoxicity, stability, chitosan nanoparticles, and polyethylene glycol ( Figure 2D ). Module 5, “carbon_dots”, includes 13 keywords, such as floating hydrogel, classification, and cyclodextrin ( Figure 2E ). Finally, Module 6, “pathway”, encompasses 13 keywords, including extraction, metastasis, derivatives, and proliferation ( Figure 2F ). These modules likely represent emerging trends in hydrogels for oncology drug delivery over the next five years and potentially beyond.

A timeline visualization, based on citation time spans, identifies emerging, classic, and outdated research topics. The timeline plot of hydrogel studies in oncology drug delivery comprised 19 clusters, arranged in descending order of size ( Figure 10A ). Clusters #1 (tumor cell imaging), #2 (injectable), #4 (multispectral fluorescence), and #5 (self-assembly) represent classic topics. While not necessarily the most recent, these topics were intrinsically linked to other clusters. Clusters #6 (self-organized nanogels), #7 (elp), #9 (cytarabine), #11 (covalent cross-linking), #12 (cytarabine), #13 (in situ forming), #14 (long-term stability), #15 (bioadhesion), #16 (biodegradable), and #17 (vaccination) are considered relatively outdated, exhibiting few connections to other clusters and limited subsequent development. Clusters #0 (nanocomposite hydrogels), #3 (immunotherapy), #8 (quercetin), #10 (pancreatic cancer), and #18 (oral cancer) were emerging topics, demonstrating continued activity on the timeline since their emergence. This suggested their potential to become future research hotspots. Supplementary Table S5 ( Supplementary Materials ) provides further details on these emerging clusters. In addition, some classical papers (large nodes with red circles) played a very important role in advancing the subfields ( Figure 10B ).

Cirillo G’s 2019 publication, “Injectable Hydrogels for Cancer Therapy over the Last Decade”, was attributed to group 0 and exhibited a co-citation frequency of 99 (28). This article highlighted research efforts over the past decade focused on injectable hydrogels for cancer therapy. Many researchers are developing sophisticated injectable drug delivery systems suitable for combination chemotherapy, radiation therapy, and thermal and photothermal ablation, aiming to overcome limitations of current conventional treatments.

The study “Designing hydrogels for controlled drug delivery” (15), published by Li JY, belonged to group 3 and exhibited a co-occurrence frequency of 116. This research demonstrated the ability of hydrogels to control drug release both spatially and temporally, encompassing various drug types such as small molecule drugs, large molecule drugs, and cells. Hydrogels, possessing controlled degradability and the capacity to protect labile drugs from degradation, can be used as a platform on which interactions with encapsulated drugs occur to achieve controlled drug release. They also presented different mechanisms for the design of hydrogel drug delivery systems, especially the physical and chemical properties and the interaction of the hydrogel with the drug at the network, reticular and molecular scales. In addition, they discussed the interplay and integration of these mechanisms for precise spatiotemporal control of drug release.

Javanbakht S authored a publication titled “Doxorubicin loaded carboxymethyl cellulose/graphene quantum dot nanocomposite hydrogel films as a potential anticancer drug delivery system”, which belonged to cluster 8 and exhibited a co-occurrence frequency of 35 (29). In this study, they designed a novel hydrogel nanocomposite film with anticancer properties by incorporating graphene quantum dot (GQD) nanoparticles in carboxymethyl cellulose (CMC) hydrogel with doxorubicin (DOX) as a drug model. The prepared nanocomposite hydrogel films showed improved in vitro solubility, degradation, water vapor permeability and pH-sensitive drug delivery properties. The nanocomposite hydrogel films could be used as anticancer films and drug delivery systems.

The article “Functional hydrogels as wound dressing to enhance wound healing” by Liang YP et al. (30) was attributed to group 3. Hydrogels possess favorable biochemical and mechanical properties, offering significant advantages in wound dressing applications. This paper mainly introduced the antibacterial, anti-inflammatory, and antioxidant properties of hydrogel dressings, along with their material transport and self-healing capabilities. It also summarized the application of hydrogel wound dressing in the treatment of different types of wounds, demonstrating their effectiveness in promoting wound healing.

Shi K et al. (31) reported on the sustained co-delivery of gemcitabine and cisplatin using a biodegradable, thermo-sensitive hydrogel for synergistic combination therapy of pancreatic cancer. They developed a biodegradable, thermosensitive copolymer hydrogel for the combined delivery of gemcitabine (GEM) and cisplatin (DDP) in pancreatic cancer treatment. This hydrogel exists as a free-flowing liquid at room temperature, transitioning to a semi-solid state at physiological temperatures upon injection. In vitro and in vivo drug release studies demonstrated sustained drug release from this system. The hydrogel system exhibited a stronger synergistic therapeutic effect against pancreatic cancer, both in vitro and in vivo, compared to hydrogels loaded with single drugs.

Shi et al.’s 2017 publication, “Cancer nanomedicine: progress, challenges and opportunities” (32), was attributed to group 18. The limitations of traditional cancer therapies have spurred in-depth research into nanotechnology for more effective and safer cancer treatment, giving rise to the field of cancer nanomedicine. This study primarily reviewed the development of cancer nanomedicine, concluding that a deeper understanding of tumor biology and nanobiology is crucial for developing improved cancer nanotherapies. Analysis of the citation distribution of these five articles over recent years ( Figure 10C ) suggested that these publications were likely to continue to be cited in the future.

Conventional tumor therapy focuses on the tumor itself, but given the complexity of the tumor microenvironment, immunotherapy has emerged as a promising approach. Immunotherapy leverages the body’s immune system to attack tumors, wherein immune cells target and destroy tumor cells within the tumor microenvironment (40, 41). Tumor immunotherapy is a guideline-recommended treatment modality for gastrointestinal tumors, demonstrating good efficacy and fewer side effects (42). Hydrogels, capable of drug loading, controlled drug release, and delivery of immunomodulatory molecules, immune cells, and environmental regulators, can improve the overall response rate of immunotherapy. This has led to their emergence as multifunctional materials in biomedical applications (43). Yang Y et al. developed a shear-thinning injectable hydrogel that enhances local immunotherapy for gastric cancer by repolarizing tumor-associated macrophages (44). Their results demonstrated favorable tumor growth inhibition after a single injection. Similarly, Seo HS et al. developed a multifunctional ethylene glycol methacrylate-chitosan (MGC) hydrogel that effectively inhibited tumor recurrence and metastasis, enhanced immunotherapy efficacy, and minimized side effects (45). These findings indicate that hydrogel-based drug delivery systems combined with cancer immunotherapy could significantly improve local and systemic treatment outcomes, providing more precise and effective treatment strategies.

Immunogenic cell death (ICD) is a form of programmed cancer cell death wherein dying cancer cells release immune-stimulating factors, prompting the immune system to recognize and eliminate tumors (46). ICD not only promotes the release of tumor-associated antigens but also activates the immune response of T cells through the maturation of antigen-presenting cells (47). The occurrence of ICD is characterized by changes in surface molecules, the release of inflammatory factors, and antigen activation, all of which contribute to enhancing the anti-tumor response of the immune system. Studies have shown that nanomaterials can enhance tumor immunogenicity by inducing ICD, thereby improving the efficacy of immunotherapy (48). Shen et al. designed a copper (Cu)-induced injectable hydrogel. This ion-induced self-assembled hydrogel containing NO can enhance immunotherapy by amplifying ICD and regulating cancer-associated fibroblasts (49). A pH-responsive polyamidoamine dendritic nanocarrier-incorporated hydrogel can serve as a drug delivery system to bind immunochemotherapy drugs, induce immunogenic cell death-related cytokines, and trigger CD8⁺ T cell-mediated immune responses to enhance immunogenic cell death and reverse immunosuppression, leading to significant tumor growth inhibition (50). An in-depth study of ICD will improve our understanding of the role of hydrogel drug delivery systems in the tumor immune microenvironment and facilitate the development of more effective immunotherapy strategies.

Cellulose, a renewable polymer, and its derivatives are widely used in various medical applications, including tissue engineering, artificial blood vessels, and drug carriers, with many applications related to the treatment of cancer (51). Carboxymethyl cellulose (CMC), a readily available chemical product, possesses thickening and relative stability properties, making it an ideal hydrogel carrier (52). This hydrogel exhibits biocompatibility, biodegradability, and antibacterial properties. CMC hydrogel can deliver the anticancer drug 5-fluorouracil, and adjusting the electric field can influence the drug’s diffusion coefficient, enabling precise drug release (53). Combining CMC with other materials can further enhance hydrogel properties. Nano-composite hydrogel beads formed by combining CMC with starch and ZnO nanoparticles have been investigated for the controlled release of doxorubicin. This composite material can prolong the drug release and control it more accurately by adjusting the content of ZnO nanoparticles (54). Nanocomposite hydrogel beads composed of CMC, starch, and zinc oxide nanoparticles (ZnO-NPs) have also been studied for the controlled release of doxorubicin. Increasing the ZnO nanoparticle content can prolong drug release time, and this composite has also demonstrated toxicity to human colon cancer cells in vitro (54). CMC-based hydrogels have diverse applications in drug delivery systems and can achieve precise drug release control and enhanced biocompatibility through various combinations and modifications.

In recent years, with increased understanding of tumor biology, tumor-targeted drugs have seen rapid development in cancer treatment. However, viral reactivation can occur in patients undergoing targeted therapy (55), necessitating viral prophylaxis and anti-inflammatory measures post-treatment. The development and design of bioactive materials with both anti-tumor and anti-bacterial properties has gained attention due to the established link between bacteria and tumors. Antimicrobial hydrogels possess excellent antimicrobial properties, good biocompatibility, water absorption and retention, and high oxygen permeability, making them widely applicable in biomedicine, smart textiles, cosmetics, and medical dressings (56, 57). By modifying the properties of hydrogel, its antibacterial, vascularization, anti-inflammatory and antioxidant properties can be enhanced (58). In one study, a nanocomposite dual network (NDN) hydrogel with tumor-targeting effects was found to improve the therapeutic efficacy of radiation therapy and eliminate potentially pathogenic bacteria to prevent postoperative wound infections (59).

Chitosan, the only naturally occurring alkaline polysaccharide, is derived from chitin through deacetylation and possesses immunomodulatory, anti-cancer, and lipid metabolism-regulating properties (60). Its favorable biocompatibility, biodegradability, and blood compatibility make chitosan hydrogels widely applicable in medicine (61). One study developed a chitosan-based thermosensitive hydrogel containing adriamycin liposomes for localized cancer therapy. This hydrogel rapidly forms a gel at body temperature, significantly enhancing anti-tumor activity while reducing systemic toxicity (62). A modified chitosan thermosensitive hydrogel, administered via intratumoral injection, achieves sustained paclitaxel release and significantly enhances anti-tumor activity (63). Composite hydrogels, formed by combining chitosan with other materials, exhibit excellent drug-release properties and biocompatibility. For example, oxyamino chitosan, as a co-delivery carrier for genes and drugs, effectively facilitates anti-cancer therapy (64). Combining and functionally modifying chitosan hydrogels with other materials to enhance their potential in drug delivery systems leads to more effective oncology drug therapy.

Nanoscale drug delivery systems enhance the retention, accumulation, and penetration of immunotherapeutic drugs at the tumor site, while also enabling controlled drug release. Incorporating micron- and nanoscale materials into hydrogels can improve their mechanical and functional properties, resulting in composite gels. Nanohydrogels can be classified as either conventional or environmentally responsive based on their phase transition mechanisms (65). Environmentally responsive nanohydrogels can respond to various external stimuli, enabling controlled drug release, enhanced penetration and retention of chemotherapeutic drugs, and improved therapeutic efficacy (65). Furthermore, combining nanohydrogels with gene therapy via intelligent drug delivery systems can further enhance tumor therapy effectiveness (66). Composite hydrogels are versatile and tunable, finding wide applications in tumor model reconstruction, tumor diagnosis, and tumor therapy.

Injectable hydrogel systems have applications in the postoperative management of tumors (67). Implantable hydrogel scaffolds can be designed for drug release or to facilitate immune cell infiltration. For example, an injectable, thermosensitive hydrogel based on black phosphorus nanosheets and adriamycin has been developed for photothermal chemotherapy of bone tumors, which can continuously release adriamycin to improve the anti-tumor efficacy and reduce systemic toxicity (68). Injectable hydrogels, prepared using appropriate physical and chemical crosslinking methods, possess both injectability and self-healing capabilities, achieving a balance between ease of preparation and material functionality. At present, clinically used hydrogel products are primarily administered via oral mucosa, oral, vaginal, transdermal, and ocular routes (69).