Helical nanoparticles trigger cancer alarms and deliver gene therapy
Cancer cells survive by hiding from the immune system's surveillance. A KAIST research team has developed a new anticancer platform that makes cancer cells send out their own danger signals—prompting immune cells to attack—while simultaneously delivering gene therapy. The approach is expected to offer a new treatment 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. A polypeptide is a polymer made of a long chain of amino acids.
A team led by Professor Yeu-Chun Kim from the KAIST Department of Chemical and Biomolecular Engineering developed a "helical polypeptide nanoparticle" platform that induces severe stress inside cancer cells to trigger immunogenic cell death while also delivering a range of gene therapeutics into the cells. The findings are published in the journal Biomaterials.
How the helical shape helps
The body's immune cells effectively eliminate external invaders such as viruses and bacteria, but cancer cells evade immune surveillance through a variety of immune-escape strategies. This failure 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 exploring 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 induce cellular stress and activate antitumor immune responses.
By comparing and analyzing a range of nanoparticles, the team confirmed that not just the chemical composition but the helical, coiled shape of the nanomaterial is a key factor determining therapeutic efficacy.
In particular, when a positively charged quaternary amine—a chemical structure that binds readily to cell membranes—was combined with a helical structure, the particle could penetrate the cell membrane like a screw and enter cancer cells with ease. By contrast, particles with the same chemical composition but lacking the helical coil barely entered cells and failed to induce an immune response.
Forcing cancer cells to signal danger
The helical nanoparticles developed by the team preferentially seek out and penetrate cancer cells, which have different membrane electrical properties from normal cells. Once inside, the particles disrupt the membranes of mitochondria—the cell's energy-producing organelles—and other organelles, subjecting the cancer cell to severe stress.
Under this extreme stress, the dying cancer cell releases damage-associated molecular patterns (DAMPs)—distress signals indicating "a dangerous cell is here"—into the surrounding environment. Immune cells that detect these signals recognize the previously hidden cancer cell as a threat and begin their attack. In effect, the cancer cell is made to broadcast its own location to the immune system.
Carrying RNA into the cell
The nanoparticle does more than trigger an immune response—it also functions as a carrier for gene therapeutics. 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.
The team's nanoparticles, however, delivered these molecules effectively into the cytoplasm.
The researchers also introduced guanidinium, a chemical functional group that binds strongly to genetic material, at an optimized ratio, enabling the particles to remain stable in the bloodstream while delivering gene therapeutics effectively.
Tumor suppression in mice
In mouse models of melanoma and colorectal cancer, the team loaded the helical nanoparticles with siRNA targeting PD-L1 (Programmed Death-Ligand 1), an immune-evasion protein, and administered them. Tumor growth was suppressed by approximately 70%–80%, and a marked increase was observed in cytotoxic T cells—which directly attack cancer cells—infiltrating the tumor, indicating a substantial boost in antitumor immune response.
"This study presents a new anticancer platform in which the nanomaterial does more than simply deliver a therapeutic agent—it drives cancer cells to trigger their own immune response," Kim said. He added that the platform is expected to contribute to the development of next-generation treatments combining cancer immunotherapy and gene therapy.
Dr. Susam Lee, the paper's first author, added, "We showed that it is not just the composition of the nanomaterial but the helical structure itself that is the key factor determining therapeutic efficacy." He said he hopes the findings will serve as a new benchmark for designing next-generation immuno-oncology nanomaterials.
Publication details
Susam Lee et al, Helical quaternary amine polypeptide programs membrane stress to drive immunogenic cell death and cytosolic gene delivery for cancer immunotherapy, Biomaterials (2026). DOI: 10.1016/j.biomaterials.2026.124337
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Citation: Helical nanoparticles trigger cancer alarms and deliver gene therapy (2026, July 28) retrieved 28 July 2026 from https://phys.org/news/2026-07-helical-nanoparticles-trigger-cancer-alarms.html
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