Targeted cancer therapeutics are becoming a reality thanks to Brown University's contribution of the new hydrogel - the shuttle for chemotherapy.

Two problems, one solution.

Here is Brown's breakthrough: A team of biomedical engineers from Brown University has developed a new hydrogel-based delivery system that balances the acidic environment in a tumor and greatly enhances the cancer-fighting activity of the chemotherapeutic drug it encapsulates in lab experiments.

This team of innovative minds have created a system that can help thousands of patients with cancer. That means improving the lives of our loved ones.

Understanding Cancer and Its Challenges

Cancer is a group of malignant cells that can detach from their original position and spread to any part of the human body—this process is called metastasis. Cancer is usually formed by an incorrect mutation of the cell during mitosis (cell division). These mutations happen every day in all of our bodies, and there is a natural and incredible adaptation that helps us not develop cancer: apoptosis and cell-to-cell communication. As a gene mutates, the cell identifies this and kills itself so that it does not cause damage. A patient who has developed cancer must have had an issue with this process of apoptosis (programmed cell death), caused by factors such as radiation, age, chemicals, and more.

A common issue with cancer is its metastasis, the process in which a malignant group of cells move away from the origin of the cancer and spreads to different areas in the body. This leads to a more complex treatment process for the patient. The Brown team of scientists began to pay close attention to this event and identified the factors that lead to this metastasis. They targeted a specific variable: the decrease in pH levels around the tumorous cells.

The pH Problem: A New Discovery

Around cancerous cells there is a lower pH (more acidic environment), and this enhances the detachment of cells so that they spread throughout the body. This is what Brown University first wanted to solve. They developed a hydrogel, which is a polymer solution. Hydrogels are used in hygiene products and contact lenses and can now be used for drug release.

They developed the hydrogel solution in a certain shape and form so that it balances the pH surrounding the cell and deals with metastasis of the cancer.

But what is another issue with this change in pH? Medicine efficiency.

Doxorubicin is a common cancer therapy. This therapy, when it is in an acidic environment, gets trapped outside of cells through a process called "ion trapping." So as cancerous cells change their pH to become more acidic, this therapy is no longer effective to reduce the patient's cancer. That is the real purpose of this hydrogel: to help increase the pH surrounding the cancerous cells and facilitate the doxorubicin's entry into the cells to destroy them.

"What we're trying to do is to develop a method to locally deliver doxorubicin but also mitigate acidosis at the same time," said Zahra Ahmed, lead study author. "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."

Problem Two: Non-Targeted Delivery

A common solution to treat cancer is chemotherapy. This medication is commonly inserted intravenously—as this makes it more effective for the body to absorb—and flows to every cell in the body. That's the issue. Chemotherapy is non-specific; it does not have a target cell to kill, when we would need it to target only the cancerous cells. So Brown began ideating: if we know where the tumor is located, then can't we just deliver the chemotherapy right to that area? The bloodstream is magnificent at the spread of general body drugs—whether that's a painkiller or anesthesia, for example. But when it comes to targeted location, we need stability and precision, which the bloodstream does not provide.

The team asked: "Can we deliver doxorubicin locally using the same delivery vehicle?"

Creative Problem-Solving: The "Yes, And" Approach

There is a fundamental creative tool that I learned from The Imagination Emporium, and that is the "Yes, and" tool. I say it is fundamental because this builds the basis of a creative idea. At this point, Brown's team had developed the hydrogel, and in their ideation process they may have sat down to build on this idea or perhaps to build on a previous idea with new creation. Using the tool of "yes, and" works best in teams. Here, scientists had the hydrogel to increase pH acidification around the cells, now they could first accept this idea (Yes) and build on it (and). For example, "Yes, and we could make the hydrogel stick to the cancerous cells and surround them. Yes, and we could use the hydrogel as a way to deliver therapy and break down cancer. Yes, and we could insert a therapeutic inside the hydrogel so that it delivers it directly."

To be creative, the team had to be brave. Now results and innovation have rewarded their bravery.

The Complete Solution

So they used the already-created biocompatible hydrogel as a private shuttle for the chemotherapeutic to arrive exactly at the cancerous cells. Not only did it arrive at the tumor and release the therapeutic, but it enhanced its entrance to the malignant cells. Remember, the hydrogel they created balanced the pH levels of the surroundings, which helped reduce metastasis and improve therapy absorption. Now the chemotherapy can be delivered specifically to the target location with the use of a buffer such as this pH-balancing hydrogel.

The results show a reduction in harsh therapy applied intravenously to the human body, quicker recovery after therapy, and overall, most importantly, more targeted delivery to attack cancerous cells.

It's incredible how we can combine innovations to impressively improve patient outcomes.

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This breakthrough research from Brown University demonstrates how creative engineering solutions can address multiple problems simultaneously, offering hope for more effective and less harmful cancer treatments in the future.