The Role Of Biological Carbon Dots In Erythroid Development And Its Application In The Treatment Of Anemia

Anemia is a global public health problem,which has a major impact on human health and socio-economic development.With the increase of global aging and the high incidence of tumors and related diseases,this problem has become more and more prominent.There are only three possible causes of anemia: decreased RBC production,increased RBC destruction,and blood loss.In the drug treatment of anemia,Erythropoietin(EPO)is a common clinical agent used to cure various types of anemia,especially in the treatment of cancer-related anemia.However,many studies have proved that EPO can promote tumor proliferation and metastasis,thereby increasing the mortality of patients.Therefore,there is an urgent need to develop new effective drugs to treat cancer-related anemia.Carbon dots(CDs)are a new type of carbon nanomaterials with a size less than 10 nm.With low toxicity,high biocompatibility,cell membrane permeability,etc.,it is widely used in the biomedical field.In recent years,with the deepening of exploration,CDs from a variety of biological sources have been found to be directly used as drugs for the treatment of diseases,showing great potential for drug development.In the early stage of this project,a variety of different biological CDs were prepared by hydrothermal method,and with the help of the in vitro culture system for inducing erythroid differentiation to screen,and the final screening was obtained a biological CDs(named: J-CDs).It can significantly promote the proliferation of erythroid cells.And then the structure,optics,stability,and biological properties of JCDs were studied.We found that J-CDs were successfully prepared by hydrothermal method,and have the characteristics of biocompatibility,cell membrane permeability,good fluorescence stability and hydrophilicity.Flow cytometry detection and colony formation experiments had shown that J-CDs promote the proliferation of erythroid cells via stimulating self-renewal of erythroid progenitors,using an in vitro erythroid differentiation system.Besides,J-CDs not affect the terminal differentiation and enucleation of erythroid cells.Then,we use wild-type mice with C57BL/6N background to explore the effect of J-CDs on erythroid development in vivo,and we found that J-CDs promoted the increase of red blood cells(RBC),hemoglobin(HGB),and hematocrit(HCT),but did not affect white blood cells in peripheral blood.And JCDs increased the proportion and absolute value of Ter119+ cells in mouse bone marrow and spleen via induce self-renewal of erythroid progenitors.Importantly,when we investigated the influence of J-CDs on tumor progression in cell and Xenograft mouse model of ovarian cancer,we found that J-CDs had no discernible effects on tumor proliferation and metastasis compared with EPO.Transcriptome profiling suggested that J-CDs upregulated molecules involved in signal transduction.Besides,J-CDs significantly upregulated the expression and phosphorylation level of STAT5,the major transducer of signals for proliferation of erythroid progenitor cells.Taken together,our research shows that J-CDs effectively promotes erythropoiesis by enhancing the self-renewal of erythroid progenitor cells without affecting tumor proliferation and migration.It is a promising anti-anemia drug for cancer patients.Cancer-related anemia provides new options and directions.At the same time,the research of this topic provides data support for the research of other CDs in the erythroid development.