Advances in Research on Precise Biological Targeting Mechanisms of Nanomaterialsgeting Mechanisms of Nanomaterials
Li Hongchang's research group at the Nanomedicine Technology Research Center of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Yu Xuefeng's research group at the Material Interface Research Center and Li Yang's research group at the Polymer Drug Research Center discovered a new mechanism for precision biomolecular targeting of nanomaterials. The relevant research results were published in Nature Nanotechnology under the title Intrinsic Bioactivity of Black Phosphorus Nanomaterials on Mitotic Centrosome Destabilization through Suppression of PLK1 Kinase.
The team selected black phosphorus nanomaterials as the research object, and fine cell biology and molecular biology studies found that nanomaterials can accurately target a specific biomolecule in cells to obtain specific biological effects. The study provides a brand-new paradigm for in-depth exploration of precise biological targeting mechanisms of nanomaterials from the dimension of molecular cell biology.
With the widespread application of nanotechnology, understanding nanobiological effects and safety has become increasingly important, and related research is always in its early stages. Nanobiological action can have both positive and negative effects. Positive nanobiological effect can be used to develop new nanomedicines, which will bring new opportunities for disease diagnosis and treatment; negative nanobiological effect, which has toxicity to the human body, organisms and even the entire ecological environment, will cause serious biological safety hazards. Studying the mechanism of action of nanomaterials and biological systems, especially at the cellular and molecular levels, is essential for the correct application of nanotechnology.
It has been found that treatment of cells with low concentrations of black phosphorus nanomaterials can lead to specific arrest of cell division in the mitotic M phase of the cell cycle. The whole cell cycle is divided into four periods, each division strictly follows the order of G1, S, G2, and M. Each process is finely regulated by numerous signaling pathways. Black phosphorus nanomaterials lead to cell cycle arrest in the M phase with the shortest time course in the cell cycle, meaning that nanomaterials specifically interfere with a key organelle or a key signaling pathway function in the M phase, and thus may be a material-specific nanobiological effect. The team deeply explored the mechanism behind the phenomenon and found that black phosphorus nanomaterials caused the separation of the mitotic core organelle, the centrosome, to be blocked. The mechanism is determined to be the direct cause of M phase arrest of cell division caused by black phosphorus nanomaterials.
The cell cycle blocking effect caused by black phosphorus nanomaterials is comparable to the discovered specific small molecule drugs targeting the M phase of cell division, and the scientific research team further explored whether black phosphorus nanomaterials have specific biological targeted molecules. Through a series of biochemical and cell biological studies, the researchers confirmed that the mitotic kinase PLK1 is a biological effect target of black phosphorus nanomaterials. Black phosphorus nanomaterials can specifically bind PLK1 and inhibit its kinase activity, thereby blocking the normal progression of M phase of cell division.
Inhibition of the cell cycle is an ideal antitumor strategy. As a novel PLK1 inhibitor, black phosphorus nanomaterials show excellent tumor inhibition effects in experimental animal models. Black phosphorus nanomaterials may develop into clinically available anti-tumor nanomedicines. This study clearly shows that nanomaterials can obtain specific nanobiological effects by accurately targeting specific biomolecules, which will drive the nano field to carry out research on the intrinsic biological effects and molecular cellular mechanisms of different nanomaterials, and open up a brand-new path for nanomedicine research and development.
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