A major bibliometric study analyzing over 4,000 publications has mapped the explosive growth of hydrogel-based drug delivery systems in cancer therapy, revealing how these flexible materials could revolutionize precision oncology treatment by offering safer, more targeted therapeutic approaches.
The comprehensive analysis, published in Frontiers in Immunology, examined 4,108 research articles spanning 2000 to 2024, demonstrating unprecedented growth in hydrogel cancer research. Annual publications increased dramatically from just five papers in 2000 to over 613 in 2024, with the steepest acceleration occurring after 2016.
Revolutionary Drug Delivery Platform
Hydrogels represent a paradigm shift from conventional cancer therapies that often cause severe systemic toxicity due to their non-specific targeting. These hydrophilic polymers form three-dimensional network structures capable of harboring both water and drug molecules, enabling precise control over drug release timing and location.
"Injectable hydrogels offer an innovative and minimally invasive chemotherapy delivery system that carries drugs to the tumor without entering the systemic circulation," the researchers noted. The hydrogel formulation helps drugs penetrate better and remain at the active site for extended periods through both passive diffusion and active transport mechanisms.
Unlike traditional chemotherapy that affects healthy cells throughout the body, hydrogels can be engineered to release drugs specifically within the tumor microenvironment. pH-sensitive nanosystems, for example, trigger drug release in the acidic conditions characteristic of tumor tissue, significantly improving therapeutic efficiency while minimizing off-target effects.
Global Research Landscape
The bibliometric analysis revealed China leading global research output, followed by the United States and India. The Chinese Academy of Sciences and Sichuan University emerged as the most productive institutions. However, the study identified limited international collaboration depth, suggesting opportunities for enhanced cross-border research partnerships.
The International Journal of Biological Macromolecules published the highest number of articles (193), followed by the Journal of Drug Delivery Science and Technology (101) and the Journal of Controlled Release (98). These journals represent key venues for researchers tracking developments in hydrogel-based cancer therapeutics.
Emerging Therapeutic Applications
Current research hotspots identified through keyword analysis include several breakthrough areas. Immunotherapy applications represent a major frontier, with hydrogels serving as delivery platforms for immune cells and immunomodulatory molecules. These systems can enhance local immunotherapy for gastrointestinal tumors, which represent guideline-recommended treatments with demonstrated efficacy and fewer side effects.
Immunogenic cell death (ICD) mechanisms have gained significant attention, with hydrogels designed to induce this specialized form of programmed cell death. ICD not only promotes tumor-associated antigen release but also activates T cell immune responses through antigen-presenting cell maturation. Copper-containing hydrogels, for instance, can enhance immunotherapy by amplifying ICD and regulating cancer-associated fibroblasts.
Advanced Material Innovations
Carboxymethyl cellulose (CMC) has emerged as an ideal hydrogel carrier due to its biocompatibility, biodegradability, and antibacterial properties. CMC hydrogels can deliver anticancer drugs like 5-fluorouracil with precise release control achieved through electric field adjustments. Nanocomposite combinations with zinc oxide nanoparticles have demonstrated enhanced controlled release capabilities for doxorubicin delivery.
Chitosan-based systems represent another major advancement, offering natural alkaline polysaccharide properties with immunomodulatory and anti-cancer effects. Modified chitosan thermosensitive hydrogels achieve sustained paclitaxel release while significantly enhancing anti-tumor activity through intratumoral injection approaches.
Multifunctional Treatment Platforms
The development of antimicrobial hydrogels addresses the critical need for materials with both anti-tumor and antibacterial properties. These systems possess excellent antimicrobial characteristics while maintaining good biocompatibility, water absorption, and oxygen permeability. Nanocomposite dual network hydrogels with tumor-targeting effects can improve radiation therapy efficacy while eliminating potentially pathogenic bacteria to prevent postoperative infections.
Injectable hydrogel systems offer particular promise for postoperative tumor management. These formulations exist as free-flowing liquids at room temperature but transition to semi-solid states at physiological temperatures upon injection. Black phosphorus nanosheet-based injectable hydrogels combined with adriamycin have demonstrated effectiveness in photothermal chemotherapy for bone tumors.
Future Research Directions
Timeline visualization analysis identified five emerging research clusters likely to dominate the next five years: peritoneal carcinomatosis applications, iron oxide nanoparticle integration, advanced drug delivery mechanisms, release kinetics optimization, and carbon dot incorporation.
The study revealed that while hydrogels are not yet in widespread clinical use for cancer treatment, they continue gaining traction as promising platforms for precise, localized, and multifunctional drug delivery. Current clinical applications primarily utilize oral mucosa, oral, vaginal, transdermal, and ocular administration routes.
Clinical Translation Challenges
Despite significant research progress, the field faces several limitations. Most institutional collaborations remain within national boundaries, limiting international knowledge exchange. Additionally, the reliance on single database sources and varying analysis methodologies may introduce research bias.
The researchers emphasized that high-quality recent publications may show low citation counts due to their recent publication dates, requiring continued monitoring as the field evolves. However, the consistent upward trajectory in publication numbers and research quality suggests robust continued growth in hydrogel-based cancer therapeutics.
This comprehensive analysis provides researchers with valuable guidance for future hydrogel applications in oncology, highlighting the technology's potential to transform cancer treatment through safer, more effective targeted drug delivery systems.
