Scientists at the University of North Carolina and North Carolina State University have developed an injectable polymer hydrogel that breaks down in response to reactive oxygen species (ROS) produced by tumor cells. During its controlled degradation, the hydrogel releases a chemotherapeutic drug and an immunotherapy to kill surrounding tumor cells.
Cancer immunotherapies have shown significant promise in treating a variety of cancer types. However, some cancers lack the characteristics that make immunotherapies effective, and these are called low-immunogenic tumors. One way to make immunotherapies more effective involves treating tumors with chemotherapy drugs first, but this technique has still not made immunotherapies effective for low-immunogenic tumors using conventional drug delivery techniques.
One way to enhance the effectiveness of anti-cancer treatments is to deliver them directly into a tumor. By incorporating a treatment into a hydrogel and then injecting it directly into a tumor, the therapeutic compound is released slowly over time in the area where it is most needed, and produces fewer side-effects elsewhere in the body.
The North Carolina group of researchers has developed an advanced bioresponsive polymer hydrogel delivery vehicle to address the problem of low-immunogenic tumors. “The trick is that the gel can be formed quickly inside the body once a biocompatible polymer and its crosslinker are mixed together,” said Jinqiang Wang, a researcher involved in the study. “We made sure that one of these agents can be cleaved apart by reactive oxygen species, or ROS – a natural chemical byproduct of cell metabolism.”
High levels of ROS are a characteristic of the rapid growth found in tumors, meaning that the hydrogel degrades and releases its therapeutic payload specifically in response to the tumor environment. The researchers load the hydrogel with a chemotherapeutic drug and an immunotherapeutic agent. In response to ROS, the hydrogel breaks down, releasing the chemotherapeutic first, which primes the tumor for the second wave of therapy, the immunotherapeutic.
In animal tests, the gel therapy was effective at reducing the size of low-immunogenic 4T1 breast cancer tumors, suggesting the treatment may have potential in humans for cancers that do not respond to conventional immunotherapies.
Study in Science Translational Medicine: In situ formed reactive oxygen species–responsive scaffold with gemcitabine and checkpoint inhibitor for combination therapy…