An American team has created an injectable gel-like scaffold that can hold combination of chemotherapeutic and immunotherapeutic drugs and deliver them locally to tumors in a sequential manner.
The findings, published on Wednesday in the journal Science Translational Medicine, could potentially ramp up therapeutic benefits one day for patients bearing tumors or after removal of the primary tumors.
The research has been done on the animal model of mice, the researchers told Xinhua. It focused on two specific types of melanoma and breast cancer, but this approach could work in other tissue types.
The results showed that the localized delivery of combination therapy significantly inhibited the recurrence of cancer after the primary tumor was surgically removed.
"We've created a simple method to use chemotherapy while leveraging the biology of the tumor and our natural defense against foreign invaders to beat back tumor development with limited side effects," said the paper's senior author Gu Zhen, an associate professor from the University of North Carolina.
Researchers developed a bio-responsive scaffold system. It is a hydrogel, a polymeric network that can transport drugs and immunotherapy directly to the tumor site to enhance treatment efficacy and decrease toxicity in other parts of the body.
"The trick is that the gel can be formed quickly inside the body once a biocompatible polymer and its crosslinker are mixed together," said co-lead author, Wang Jinqiang, a postdoctoral researcher in Gu's lab.
Researchers loaded the hydrogel scaffold with a chemotherapeutic drug gemcitabine and an anti-PD-L1 blocking antibody, a kind of immunotherapeutic agent.
When injected into the tumor, the gel promotes the kinds of tumor characteristics that immunotherapies can identify.
Those characteristics include the reactive oxygen species (ROS), a major player in tumor development and growth.
In response to the highly abundant ROS, the scaffold gradually breaks down, releasing gemcitabine first, and then anti-PD-L1 agent.
"We made sure that one of these agents can be cleaved apart by reactive oxygen species, a natural chemical byproduct of cell metabolism," said Wang.
Gu's team tested two cancers, a melanoma and a kind of breast cancer that is low immunogenic. When the payload was released, tumors decreased significantly.
The researchers then conducted experiments to have the hydrogel scaffold form at the surgical site after removal of primary tumors. They witnessed a remarkable inhibition of cancer recurrence.
"We have a lot more work to do before human clinical trials, but we think this approach holds great promise," Gu said.