Intranuclear Nanoribbons for Selective Killing of Osteosarcoma Cells. (5th October 2022)

• Record Type: Journal Article
• Authors: Liu, Shuang; Zhang, Qiuxin; He, Hongjian; Yi, Meihui; Tan, Weiyi; Guo, Jiaqi; Xu, Bing
• Is Part Of: Angewandte Chemie. Volume 134:Number 44(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-05
• Subjects: Alkaline Phosphatase -- Enzyme Instructed Self-Assembly -- Histone Protein -- Nuclear Targeting -- Osteosarcoma Cells; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202210568
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: Herein, we show intranuclear nanoribbons formed upon dephosphorylation of leucine‐rich L‐ or D‐phosphopeptide catalyzed by alkaline phosphatase (ALP) to selectively kill osteosarcoma cells. Being dephosphorylated by ALP, the peptides are first transformed into micelles and then converted into nanoribbons. The peptides/assemblies first aggregate on cell membranes, then enter cells via endocytosis, and finally accumulate in nuclei (mainly in nucleoli). Proteomics analysis suggests that the assemblies interact with histone proteins. The peptides kill osteosarcoma cells rapidly and are nontoxic to normal cells. Moreover, the repeated stimulation of the osteosarcoma cells by the peptides sensitizes the cancer cells rather than inducing resistance. This work not only illustrates a novel mechanism for nucleus targeting, but may also pave a new way for selectively killing osteosarcoma cells and minimizing drug resistance. Abstract : Upon the dephosphorylation of ALP, the leucine‐rich phosphopeptides self‐assemble into micelles and then convert into nanoribbons. The phosphopeptides/assemblies first aggregate on the cell membrane of osteosarcoma cells, and then enter cells via endocytosis, disrupt the nuclear membrane, and finally accumulate in nuclei by interaction with histone proteins to induce cell death.