Intranuclear assembly of leucine-rich peptides for selective death of osteosarcoma cells.
Shuang LiuQiuxin ZhangXingrao PengCong HuShao-Wei WangYao SunPublished in: Biomaterials science (2024)
Herein, we show a pair of leucine-rich L- and D-phosphopeptides which self-assemble into twisting nanofibers, whose secondary structures contain a strong β-sheet component after being dephosphorylated by alkaline phosphatase (ALP). While being incubated with ALP overexpressing osteosarcoma cells, both of the peptides self-assemble in the nuclei and induce cell death. The cell death involves multiple cell death modalities and occurs along with the disruption of cell membranes. Enzyme-instructed self-assembly (EISA) inhibits osteosarcoma cells and shows no side effect to other cells. In addition, the cancer cells hardly gain drug resistance after repeated treatment. This work reports a pair of EISA-based nanofibers to target cell nuclei, and also provides a novel chemotherapeutic agent to inhibit osteosarcoma cells without side effects and drug resistance.