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Intranuclear Nanoribbons for Selective Killing of Osteosarcoma Cells.

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.

SUBMITTER: Liu S

PROVIDER: S-EPMC9869109 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Intranuclear Nanoribbons for Selective Killing of Osteosarcoma Cells.

Liu Shuang S Zhang Qiuxin Q He Hongjian H Yi Meihui M Tan Weiyi W Guo Jiaqi J Xu Bing B

Angewandte Chemie (International ed. in English) 20221005 44

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 assembl ...[more]

PMID: 36102872

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