KAIST Develops Helical Polypeptide Nanoparticle That Forces Cancer Cells to Signal Their Own Destruction
核心洞察
A KAIST (搜索) research team developed a helical polypeptide nanoparticle platform that triggers immunogenic cell death while simultaneously delivering gene therapies into cancer cells.
The helical structure, combined with a positively charged quaternary amine, enables the nanoparticle to penetrate cancer cell membranes like a screw, preferentially targeting malignant cells over normal cells.
In mouse models of melanoma (搜索) and colorectal cancer (搜索), siRNA-loaded nanoparticles targeting PD-L1 (搜索) suppressed tumor growth by 70–80% and significantly increased cytotoxic T cell infiltration.
A KAIST (搜索) research team has engineered a nanoparticle platform that compels cancer cells to broadcast their own location to the immune system while simultaneously delivering gene-silencing payloads—a dual-action strategy that suppressed tumor growth by 70–80% in preclinical models of melanoma (搜索) and colorectal cancer (搜索).
The work, led by Professor Yeu-Chun Kim from the Department of Chemical and Biomolecular Engineering at KAIST (搜索), was published online in Biomaterials on May 28, 2026. The platform centers on a "helical polypeptide nanoparticle" designed to induce immunogenic cell death (ICD)—a process in which dying cancer cells release damage-associated molecular patterns (DAMPs) that alert nearby immune cells to attack.
The helical advantage: shape matters as much as chemistry
By systematically comparing a range of nanoparticles, the team demonstrated that therapeutic efficacy depends not merely on chemical composition but critically on the helical, coiled architecture of the nanomaterial. When a positively charged quaternary amine—a chemical structure that readily binds to cell membranes—was combined with a helical configuration, the particle could penetrate the cell membrane "like a screw," entering cancer cells with ease. Nanoparticles with identical chemical composition but lacking the helical coil barely entered cells and failed to elicit an immune response.
"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," said Dr. Susam Lee, the paper's first author.
The helical nanoparticles preferentially seek out cancer cells because malignant cells possess membrane electrical properties distinct from those of normal cells. Once inside, the particles disrupt the membranes of mitochondria and other organelles, subjecting the cancer cell to severe endoplasmic and oxidative stress. Under this duress, the dying cell releases DAMPs—effectively a distress beacon—that enables immune cells to recognize the previously hidden malignancy as a threat.
Dual functionality: immune activation plus gene delivery
Beyond triggering ICD, the nanoparticle functions as a carrier for gene therapeutics. The platform successfully delivered both messenger RNA (mRNA), which carries genetic information for protein synthesis, and small interfering RNA (siRNA), which suppresses expression of specific genes, into the cytoplasm—a historically challenging feat given the instability of these molecules in circulation.
The researchers introduced guanidinium, a chemical functional group that binds strongly to genetic material, at an optimized ratio. This modification stabilized the particles in the bloodstream, enabling effective transport of gene therapies without premature degradation.
Preclinical validation
In mouse models of melanoma (搜索) and colorectal cancer (搜索), the team loaded the helical nanoparticles with siRNA targeting PD-L1 (搜索) (Programmed Death-Ligand 1), an immune-evasion protein exploited by tumors to escape immune surveillance. Tumor growth was suppressed by approximately 70–80%, and a marked increase was observed in cytotoxic T cells infiltrating the tumor tissue, 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," said Professor Kim. He added that the platform is expected to contribute to the development of next-generation treatments combining cancer immunotherapy and gene therapy.
Dr. Lee expressed hope that the findings "will serve as a new benchmark for designing next-generation immuno-oncology nanomaterials."
The failure of immune cells to recognize cancer cells as threats has long been one of the most significant limitations in oncology. By engineering a single nanoparticle that both exposes hidden tumors to immune attack and delivers gene-silencing cargo, the KAIST (搜索) team offers a potential path toward more integrated and potent cancer treatment strategies.