Brown University biomedical engineers developed a hydrogel delivery system that regulates tumor acidity, significantly increasing the effectiveness of enclosed chemotherapy in laboratory tests.

To reduce side effects, an injectable hydrogel system buffers and delivers doxorubicin to tumors. It balances pH, making chemotherapy more effective and limiting cancer spread.

"At its core, the research is about mitigating some of the critical problems that we face in cancer treatment,"

said Zahra Ahmed, lead study author and Ph.D. student in the Brown lab of Assistant Professor of Engineering Vikas Srivastava.”

Acidosis has a negative impact on cancer patients' outcomes and chemotherapeutic efficacy in the tumor microenvironment. Acidic conditions increase the risk of metastasis and impair drug action. For example, doxorubicin, a well-known chemotherapy drug, becomes trapped outside cells due to acidity, reducing its ability to kill cancer.

The drug’s non-selective toxicity results in significant side effects when administered intravenously. Current methods lack the capability to balance tumor pH directly. The team’s engineered hydrogel addresses these challenges.

"What we're trying to do is to develop a method to locally deliver doxorubicin but also mitigate acidosis at the same time," Ahmed said. "To do this, we created an injectable hydrogel where we combined the delivery of the chemotherapeutic doxorubicin with something to combat the acidic pH in the local region. In this case, we used sodium bicarbonate, a chemical compound that is commonly used to treat acid indigestion."

Lab tests on breast cancer cells in vitro confirm the hydrogel’s effectiveness. It buffers with sodium bicarbonate, raising pH and boosting doxorubicin’s cancer-killing potency by 2-3 times.

Srivastava’s team spent over three years on this progressive project, initially focusing on pH regulation in the acidic tumor microenvironment.

"When we had success in pH regulation using hydrogels, which has been shown to reduce metastasis in certain cancers, we then began figuring out how to get a sodium bicarbonate delivery system to a precise tumor location," said Srivastava, whose lab at Brown's School of Engineering conducts research in solid mechanics, soft materials and mechanobiology.

"We formulated an injectable hydrogel that can be locally delivered and has the ability to regulate the pH of the tumor environment. We then wondered if we could also simultaneously deliver a chemotherapeutic. Can we deliver doxorubicin locally using the same delivery vehicle? We've now done all these things together to a great effect and have shown very promising results on two cancer cell lines in vitro."

The researchers opted for a biocompatible hydrogel as a versatile delivery system, akin to its use in contact lenses, hygiene products, and medical applications. Their developed hydrogel can be stored at 4°C for extended periods, enhancing practical medical utility.

Their next goal is pre-clinical applications, transitioning from lab experiments to animal studies and eventually human trials. Additional study contributors include Angelina Schorr, Rachel Rowey, Kevin LoGiudice, Gavin Mays, Shruti Trivedi, and Haisong Yang.