A research team led by Prof. CHEN Chunying from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences reported the mechanism of graphyne-intracellular protein interaction for the regulation of the phenotype of macrophages. The study was published in Nano Letters.
Tumor-associated macrophage (TAM) promotes tumor growth, metastasis and recurrence, and induces immunosuppression. TAM depletion, macrophage recruitment blocking, and reprogramming are useful treatments designed based on TAMs.
Nowadays, various small molecule drugs are employed in clinical trials, but small molecules lack targeting ability. Nanomaterials/nano drugs face a complex physiological environment after they entering the body and they interact with the surrounding biological fluids or biological molecules.
Nanomaterials with unique physical and chemical properties have been designed as delivery vehicles and immunomodulators to improve the tumor immunosuppressive microenvironment. Graphdiyne oxide (GDYO) as an emerging 2D carbon-network nanomaterial has offered a wide range of applications in catalysis, energy, biomedicine and other fields. It behaves in an unpredictable manner at the nano-bio interface.
In this study, the researchers used the isotope 13C to label GDYO and quantitatively analyzed the interaction ratio between GDYO and intracellular proteins. They found that a unique protein corona is formed on the surface of GDYO in macrophages which is highly enriched in signal transduction and activator of transcription (STAT3) protein.
STAT3 is an important signal transduction protein and transcription factor in cells and is closely related to the occurrence and development of tumors. By inhibiting its signal pathway, it can inhibit tumor growth and metastasis. By inhibiting the activation of STAT3 protein, GDYO reverses immunosuppressive M2 macrophages into pro-inflammatory M1 macrophages, improves the immunosuppression caused by TAMs, increases the infiltration and activation of killer T cells, and improve the efficacy of PD-L1 antibodies.
Besides, the researchers analyzed the distribution and metabolism of GDYO in peritoneal macrophages and tumors after administration. They found that the interaction at the GDYO–STAT3 interface, driven by structure matching, hydrogen bonding and salt bridges, simultaneously triggers the immune response in the tumor microenvironment.
This study explains the molecular mechanism of the unique strong interaction of GDYO-STAT3, and reveals for the first time the interaction mechanism of nanoparticle-protein interface in macrophages, which deepens the understanding of nano-biological interface regulation of complex biology.
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