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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Intranuclear Nanoribbons for Selective Killing of Osteosarcoma Cells
Shuang Liu1,2, Qiuxin Zhang2, Hongjian He2
1School of Materials Science and Engineering, Wuhan University of Technology, 122 Luoshi Road, Wuhan, Hubei, 430070, China.
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.
Insights
Novel phosphopeptides form nanoribbons that selectively kill osteosarcoma cells by targeting cell nuclei. This targeted approach offers a promising strategy to combat cancer with reduced drug resistance.
Area of Science:
- Biomaterials Science
- Cancer Biology
- Nanotechnology
Background:
- Osteosarcoma is a primary bone cancer with limited treatment options.
- Developing targeted therapies to selectively eliminate cancer cells is crucial.
- Understanding intracellular transport mechanisms is key for drug delivery.
Purpose of the Study:
- To investigate the formation and function of intranuclear nanoribbons derived from phosphopeptides.
- To evaluate the selective toxicity of these nanoribbons against osteosarcoma cells.
- To explore a novel nucleus-targeting strategy for cancer therapy.
Main Methods:
- Dephosphorylation of leucine-rich phosphopeptides catalyzed by alkaline phosphatase (ALP).
- Characterization of peptide assembly into micelles and nanoribbons.
- Cellular uptake studies using endocytosis pathways.
- Proteomics analysis to identify protein interactions within the nucleus.
Main Results:
- Dephosphorylation of phosphopeptides by ALP induces the formation of intranuclear nanoribbons.
- These nanoribbons selectively aggregate on and internalize into osteosarcoma cells, accumulating in nucleoli.
- The nanoribbons interact with histone proteins and rapidly kill osteosarcoma cells.
- Normal cells remain non-toxic, and repeated exposure sensitizes cancer cells, reducing resistance.
Conclusions:
- A novel nucleus-targeting mechanism involving phosphopeptide-derived nanoribbons has been demonstrated.
- This approach shows high selectivity for killing osteosarcoma cells.
- The strategy may offer a new avenue for cancer treatment with minimized drug resistance.
