ARIZONA — Researchers at the University of Arizona R. Ken Coit College of Pharmacy developed a strategy using lipid nanoparticles to enhance the immune response against lung cancer tumors. The findings were published in Nature Communications on June 25, 2026.

The strategy involves packaging the chemotherapy drug paclitaxel and an siRNA molecule, siSTC1, in a lipid carrier. "Since we know paclitaxel can induce ICD, we improved the delivery of the drug to the tumor by attaching a fatty molecule called a sphingolipid to form a fatty bubble, or nanovesicle," said Jianqin Lu, the John A. and Frances P. Ware Endowed Associate Professor of Pharmaceutical Sciences in the college. "We can deliver more drugs to the tumor site."

Immunogenic cell death occurs when the protein calreticulin (CRT) moves to the surface of dying cancer cells, acting as a signal that attracts phagocytes. These phagocytes engulf the dying tumor cells, which helps initiate the ICD response. However, some tumors use a molecule called STC1 to prevent CRT from reaching the cell surface, which weakens the immune response and reduces T cell activity. "Despite the significant potential of ICD-enabled immunotherapy, its therapeutic applications remain underused," Lu said.

The research team used the siSTC1 molecule to silence STC1 gene activity. The siSTC1 was co-delivered with paclitaxel. The team tested this strategy in Lewis lung cancer cells, which exhibit high STC1 gene expression, and MC38 colon cancer cells, which have lower STC1 gene expression. The combination of paclitaxel and siSTC1 was more effective against Lewis lung cancer cells than against MC38 colon cancer cells. In mouse models for lung cancer, the combination of siSTC1 and paclitaxel eradicated three out of five tumors. In some specific cancer types, the combination eradicated four out of five tumors.

"If you trigger an ICD immune response, there should be no tumor development or delayed tumor development," Lu said. The siSTC1-paclitaxel package also increased tumor sensitivity to PD-1 blockade treatment. "The paclitaxel-siSTC1 combination potentiates the PD-1 blockade therapy, and the cancer immunotherapy," Lu said. "You're really changing the tumor microenvironment."

Lu stated that the platform could potentially be used to treat cancer types with high STC1 expression, including non-small cell lung cancer, certain colon cancer types, breast cancer, liver cancer, and ovarian cancer. The team intends to collaborate with clinical oncologists to advance the platform in a phase 1 clinical trial. Several researchers co-authored the study, including Wenpan Li, Zhiren Wang, Mengwen Li, Yanhao Jiang, Shuang Wu, Leyla Cordova, and MinHyeok Kim. The journal reference DOI for the publication is 10.1038/s41467-026-72526-1.