A major new study maps the rise of hydrogels in cancer therapy, revealing how this flexible material could drive the next wave of precise, less toxic treatments.
Study: Hydrogels in cancer treatment: mapping the future of precision drug delivery. Image credit: murat photographer/Shutterstock.com
Modern cancer therapies have resulted in higher survival rates in many cases. However, their delivery mode and generic action are associated with greater adverse effects and potentially lower efficacy. A recent review published in Frontiers in Immunology analyzed the potential for introducing hydrogels in cancer treatment, which could lead to personalized, more effective, and less toxic drug delivery platforms.
Introduction
Cancer treatments include surgery, radiation therapy, chemotherapy, and traditional Chinese medicine. Chemotherapy is very commonly used to increase survival time but is associated with a range of severe adverse effects. Usually, these arise because of the off-target effects of these highly cytotoxic molecules.
Targeted drug delivery is the holy grail of cancer therapy. Newer systems are theorised which will direct drugs to act solely on the cancer cells, mediated by cell- or tumor-specific recognition mechanisms.
Nanocarriers, one promising avenue, are used to transport small-molecule cytotoxic drugs to specific cells, improving their efficiency. For instance, a pH-sensitive nanosystem releases the drug in the tumor's acidic microenvironment.
Besides ensuring more even drug distribution within the tumor, these drug delivery systems also cross biological barriers to reach intracellular targets, enhancing treatment outcomes. Hydrogels are another potential area of research in this field.
What are hydrogels?
Hydrogels are hydrophilic polymers, synthetic or natural, with a three-dimensional network structure that can harbor water and drug molecules. They can be coupled with metal-organic frameworks, forming composite materials that change their structure when exposed to different environments or stimuli.
With these properties, hydrogels have enormous potential as effective carriers for localized and sustained drug delivery to cancers. Their semisolid nature facilitates their use as transdermal carriers of antitumor drugs.
Injectable hydrogels offer an innovative and minimally invasive chemotherapy delivery system that carries drugs to the tumor without entering the systemic circulation. The hydrogel formulation also helps the drugs penetrate better and stay at the active site for extended periods, via passive diffusion and active transport across the cell membrane.
Key findings
The current study aimed to provide a comprehensive overview of the status of hydrogels in cancer treatment today. The authors analyzed 4,108 publications, mostly from China, the United States, and India, using bibliometric tools such as CiteSpace, HisCite, VOSviewer, and R, to explore trends in hydrogel-based drug delivery in cancer.
They found that the leading journal in this area (referencing the number of articles) was the International Journal of Biological Macromolecules, followed by the Journal of Drug Delivery Science and Technology and Controlled Release. As such, these are worthy of being closely followed by researchers in this field.
The analysis showed Professor Pourmadadi Mehrab as an influential researcher in this area, often collaborating with Rahdar Abbas and Pandey Sadanand. Qian Zhiyong, Zhang Yu, and their collaborators formed another close cluster. Only a few authors were highly prolific, and the field exhibited a relatively low degree of author collaboration.
The number of articles relating to this field was low initially, but increased after 2008, taking a further sharp upturn in 2016. The highest output was in 2024, with over 613 articles. This demonstrates the growth in interest in this pivotal topic.
Multiple reviews and original research articles were cited in many other publications. The single article with the highest number of citations was “Designing hydrogels for controlled drug delivery” by Li JY. This article dealt with the ability of hydrogels to regulate the distribution and time of drug release over a range of drugs, from large molecules to small molecules and cell therapies. The various designs and mechanisms they work with were also presented, including the drug-hydrogel interaction at all levels, from the network to the molecular level.
Early literature from 2000 to 2010 was found to be densely interconnected with all subsequent literature, representing its roots. From 2011 to 2017, more branches emerged, which differentiated further from 2018 to 2024. Later clusters showed increased focus on specialized applications and materials.
Shift in target research areas
The analysis revealed that work in this field began with biomedical research but has evolved to include disciplines such as Applied Chemistry, Environmental Engineering, Biochemistry, and Molecular Biology.
Collaboration was marked nationally, internationally, and between the authors who published the most in this field. China occupied the top in overall publication volume and international cooperative hydrogel research. At the same time, institutional collaborations were mainly limited to those within the same country, such as the network of Indian Institutes of Technology (IITs) in India. However, the study also noted limited depth of cross-national institutional partnerships.
The most active areas in hydrogel research were identified using keywords. Different keywords occurred over successive phases of research over the past 24 years. The 20 keywords that remained active in 2024 included “immunotherapy,” “immunogenic cell death,” “carboxymethyl cellulose,” and “antibacterial”, indicating that much future research may focus on these areas.
For instance, hydrogels can enhance immunotherapy, the recommended treatment for gastrointestinal tumors, by delivering drugs and immune cells to the cancer. Thus, hydrogels are emerging as multifunctional materials.
Hydrogels can induce immunogenic cell death by the copper they contain or by pH changes. Immunogenic cell death is a form of programmed cell death in which dying tumor cells stimulate the immune system to recognize and eliminate the tumor.
Emerging trends
In the most recent phase, core research areas include nano-composite hydrogels, immunotherapy, quercetin, pancreatic cancer, and oral cancer. Moreover, a highly cited article by Cirillo et al. (2019) reflected the intense efforts to create injectable hydrogels. While today hydrogels are primarily being studied for mucosal and local delivery, preclinical efforts are increasingly focusing on injectable systems for broader oncological applications.
The most prominent newer trends in hydrogel-based cancer drug delivery include those dealing with peritoneal carcinomatosis, iron oxide nanoparticles, drug delivery, release kinetics, and carbon dots. These may be the newer directions in hydrogel research for cancer drug delivery, at least for the next five years.
Timeline visualizations and alluvial flow maps to trace how clusters of keywords and citation activity shifted over time, showing, for example, how “tissue engineering” and “immunogenic cell death” have risen to prominence, while others have declined or fragmented.
Conclusion
This comprehensive bibliometric review identified emerging areas of future research in hydrogels for cancer drug delivery. The authors concluded, “This study provides recommendations and directions for the development of hydrogels as tumor drug delivery systems.”
While hydrogels are not yet in widespread clinical use for cancer, they continue to gain traction as a promising platform for precise, localized, and multifunctional drug delivery, with much potential in future cancer treatments.
Download your PDF copy now!
Reversing immune fatigue offers new hope for cancer treatment