Cancer cells survive by hiding from the immune system’s surveillance. A KAIST research team has developed a new anti-cancer platform that allows cancer cells to emit their own danger signals, prompting immune cells to attack them, while also providing gene therapy. This approach is expected to provide a new therapeutic strategy that combines cancer immunotherapy and gene therapy in a single nanoparticle.
Immunogenic cell death (ICD) is a process in which dying cancer cells send danger signals to nearby immune cells, prompting them to attack. Polypeptides are polymers made up of long chains of amino acids.
KAIST (Chairman Bae Choongsik) announced on July 28 that a team led by Professor Yeu-Chun Kim from the Department of Chemical and Biomolecular Engineering has developed a “helical polypeptide nanoparticle” platform that induces severe stress within cancer cells, causing immunogenic cell death, while simultaneously delivering various gene therapy drugs into the cells.
The body’s immune cells effectively eliminate foreign invaders such as viruses and bacteria, but cancer cells evade immune surveillance through various immune evasion strategies. The inability of immune cells to recognize cancer cells as a threat has long been one of the biggest limitations in cancer treatment.
Recently, researchers have been actively investigating the use of nanoparticles to deliver drugs and genes to cancer cells and activate immune responses. However, it has not been clearly established which properties of nanomaterials actually induce cellular stress and activate antitumor immune responses.
By comparing and analyzing various nanoparticles, the research team confirmed that not only the chemical composition but also the helical or coiled shape of the nanomaterials is an important factor in determining therapeutic efficacy. In particular, the combination of a positively charged quaternary amine, a chemical structure that easily binds to cell membranes, and a helical structure allows the particles to penetrate the cell membrane like a screw and easily enter cancer cells. In contrast, particles with the same chemical composition but lacking a helical coil barely penetrated cells and failed to induce an immune response.
The helical nanoparticles developed by the same team preferentially seek out and invade cancer cells, which have different membrane electrical properties than normal cells. Once inside, the particles can destroy the membranes of mitochondria and other cell organelles, the organelles that produce energy in cells, causing severe stress on cancer cells.
Under this extreme stress, dying cancer cells release damage-associated molecular patterns (DAMPs)—distress signals that indicate “danger cell here”—to the surrounding environment. Immune cells that detect these signals recognize previously hidden cancer cells as a threat and begin attacking them. In fact, cancer cells are designed to broadcast their location to the immune system.
Nanoparticles not only trigger an immune response but also act as carriers for gene therapy. Messenger RNA (mRNA), which carries the genetic information for protein synthesis, and small interfering RNA (siRNA), which suppresses the expression of specific genes, are both typically difficult to deliver into cells. But the team’s nanoparticles effectively delivered these molecules into the cytoplasm.
The researchers also introduced an optimal ratio of guanidinium, a chemical functional group that binds strongly to genetic material, allowing the particles to remain stable in the bloodstream while effectively delivering the gene therapy drug.
The researchers loaded helical nanoparticles with siRNA that targets the immune evasion protein PD-L1 (programmed death ligand 1) and administered them in mouse models of melanoma and colorectal cancer. Tumor growth was inhibited by approximately 70-80%, and a significant increase in tumor-infiltrating cytotoxic T cells (which directly attack cancer cells) was observed, indicating a significantly enhanced anti-tumor immune response.
“This study presents a new anti-cancer platform in which nanomaterials not only deliver therapeutic agents but also enable cancer cells to trigger their own immune response,” said Professor Yeu-Chun Kim.
He added that this platform is expected to contribute to the development of next-generation treatments that combine cancer immunotherapy and gene therapy.
We showed that not only the composition of nanomaterials but also the helical structure itself is an important factor determining therapeutic efficacy. ”
Dr. Susam Lee, first author of the paper
He said he hopes this discovery will serve as a new benchmark for designing the next generation of immuno-oncology nanomaterials.
This study was published online biomaterials, Leading international journal in the field of biomaterials, May 28, 2026.
sauce:
KAIST (Korea Advanced Institute of Science and Technology)
Reference magazines:
Lee, S. others. (2026). Helical quaternary amine polypeptides program membrane stress to promote immunogenic cell death and gene delivery to the cytosol for cancer immunotherapy. biomaterials. Doi: 10.1016/j.biomaterials.2026.124337. https://www.sciencedirect.com/science/article/abs/pii/S0142961226003613?via%3Dihub
