In oncology, the effectiveness of a treatment does not depend only on the drug being used. It also depends on something equally important: how that drug reaches the tumor, how long it remains there, and how limited its exposure is to healthy tissues. This question has driven the development of new local drug delivery platforms, including hydrogels, biomedical systems designed to transport and release therapeutic agents in a controlled manner.

A hydrogel is a three-dimensional polymer network with a high capacity to retain water and hold active molecules within its structure. Because of its soft texture, biocompatibility, and ability to adapt to tissue, it can function as a therapeutic matrix or depot. In the context of cancer, its purpose is not simply to “carry” a drug, but to allow that drug to be gradually released where it is needed most: inside the tumor or within its surrounding microenvironment.

This strategy responds to a frequent limitation of many systemic treatments. When a drug is administered intravenously or orally, it must circulate through the body before reaching the tumor. Along the way, it may distribute into healthy tissues, partially degrade, or cause unwanted toxicities. Local administration through hydrogels follows a different logic: to concentrate treatment in the tumor area and reduce unnecessary dispersion throughout the rest of the body.

Interest in this technology becomes even stronger when we consider the complexity of the tumor microenvironment. A tumor is not made only of malignant cells. Around it, there are blood vessels, immune cells, fibroblasts, extracellular matrix, and inflammatory or immunosuppressive signals that can influence tumor growth and treatment response. In many cases, this environment makes it harder for the immune system to recognize and effectively attack cancer cells.

Hydrogels make it possible to intervene in this microenvironment in a more localized way. They can be loaded with different therapeutic agents, such as immunomodulatory antibodies, anti-inflammatory molecules, chemotherapy drugs, adjuvants, or compounds designed to stimulate the immune response. By releasing these agents progressively, the hydrogel can maintain a sustained therapeutic concentration at the tumor site, instead of relying on brief or widely dispersed exposure.

One of the most studied approaches combines immunotherapeutic agents with drugs capable of modifying inflammatory signals within the tumor. For example, hydrogels have been evaluated for the release of anti-PD-1 together with celecoxib. Anti-PD-1 aims to block a pathway that tumors can use to suppress T-cell activity. Celecoxib, on the other hand, may modulate signals associated with COX-2 and prostaglandins, which have been linked to chronic inflammation and tumor immunosuppression. When both agents are delivered from a local matrix, the goal is to support coordinated activity within the tumor microenvironment.

This point is essential: the hydrogel should not be understood as the main anticancer treatment by itself. Its value lies in functioning as an intelligent delivery platform. It is the vehicle that allows specific drugs to remain close to the tumor, be released in a controlled manner, and act together. In this sense, hydrogels may enhance therapeutic strategies that already have a clear biological rationale but could benefit from more precise administration.

Another relevant application is related to therapeutic cancer vaccines. In cancer, a therapeutic vaccine does not always aim to prevent disease before it appears. Its purpose may be to train the immune system to recognize tumor-associated antigens and activate a response against existing malignant cells. To achieve this, antigen-presenting cells need to encounter tumor signals and stimulatory molecules in the right context.

A hydrogel can help facilitate this process by keeping antigens, adjuvants, or immune-stimulating agents concentrated in the same location. In this way, it may function as a local immune activation platform. The goal is to help immune cells capture these signals, process them, and promote the activation of T cells capable of recognizing tumor cells. This line of research aims to generate more directed and persistent immune responses, although broader clinical validation is still needed.

Hydrogels may also be useful after local procedures such as surgery or ablation. After tumor resection, a surgical bed may remain where microscopic residual tumor cells could persist. Something similar can occur after ablative techniques, where the tumor is destroyed using heat, cold, electricity, or other forms of energy. Even when the procedure reduces tumor burden, the treated area may remain a site at risk for local recurrence.

 

Figure 1. Hydrogel drug delivery system designed to concentrate therapeutic agents at the tumor site. The hydrogel matrix acts as a local depot, enabling sustained release of immunomodulatory and anti-inflammatory agents while helping reduce broader systemic exposure. 

 

In this scenario, a hydrogel could be placed in the surgical cavity or treated area to release drugs during the post-procedure period. The purpose would be to turn that vulnerable zone into a therapeutically active space. Instead of relying only on systemic drugs, the area at highest risk could receive sustained local release of anticancer or immunomodulatory agents.

Injectable hydrogels are also being investigated, a particularly important feature for deep or difficult-to-access tumors. These systems can be administered through a needle, ideally with image guidance, allowing precise placement inside or near the lesion. Some hydrogels can even respond to environmental stimuli, such as temperature, pH, enzymes, or light, making it possible to adjust their behavior once they are inside the tissue.

Despite their potential, it is important to maintain a balanced interpretation. Hydrogels are not a universal solution, nor do they automatically replace surgery, chemotherapy, radiotherapy, systemic immunotherapy, or ablation. Their usefulness depends on the type of cancer, tumor location, incorporated drug, material safety, dose, administration technique, and available clinical evidence. Many promising results come from preclinical studies, so well-designed clinical trials are still needed to define their true impact in patients.

Their importance, however, is clear: hydrogels represent a more precise way to think about cancer drug delivery. Instead of focusing only on the potency of the drug, this technology helps optimize where, when, and how the treatment is released. In precision oncology, that level of control may be just as relevant as the therapeutic molecule itself.

The future of cancer treatment will likely depend on rational combinations: image guidance, local therapies, immunotherapy, ablation, surgery, biomaterials, and personalized follow-up. Within that integration, hydrogels could play a strategic role as platforms capable of delivering therapeutic agents directly to the tumor site, sustaining their action, and modifying the microenvironment where cancer attempts to resist treatment.

In summary, hydrogels are not merely passive vehicles. They are systems designed to improve therapeutic precision, concentrate drugs within the tumor, and reduce systemic exposure. Their greatest promise lies in enabling more localized, combined, and tumor-adapted treatments. This strategy reflects an increasingly important principle in cancer care: better treatment does not always mean treating more, but treating with greater precision.

 

Main reference:

Li, Y., Fang, M., Zhang, J., Wang, J., Song, Y., Shi, J., Li, W., Wu, G., Ren, J., Wang, Z., Zou, W., & Wang, L. (2015). Hydrogel dual delivered celecoxib and anti-PD-1 synergistically improve antitumor immunity. Oncoimmunology, 5(2), e1074374. https://doi.org/10.1080/2162402X.2015.1074374 

 

Other references:

Mikhail, A. S., Morhard, R., Mauda-Havakuk, M., Kassin, M., Arrichiello, A., & Wood, B. J. (2023). Hydrogel drug delivery systems for minimally invasive local immunotherapy of cancer. Advanced drug delivery reviews, 202, 115083. https://doi.org/10.1016/j.addr.2023.115083 

Liu, Y., Geng, Y., Yue, B., Lo, P. C., Huang, J., & Jin, H. (2022). Injectable Hydrogel as a Unique Platform for Antitumor Therapy Targeting Immunosuppressive Tumor Microenvironment. Frontiers in immunology, 12, 832942. https://doi.org/10.3389/fimmu.2021.832942