Acute Myeloid Leukemia Targeted In Vivo NIR-Ⅱ Window Imaging

Acute myeloid leukemia(AML)is a heterogeneous clonal disease of hematopoietic progenitor cells and the most common malignant bone marrow disease in adults.Acute myeloid leukemia is currently a major problem that plagues mankind,and more diagnosis and treatment research is urgently needed.Glucose(Glu)is the basic substrate of metabolism in all mammalian cells,and the oxidation of glucose is an important energy source for the metabolism of eukaryotic cells.Unlike normal cells,leukemia cells,like most tumor cells,tend to metabolize glucose through glycolysis,which requires greater glucose uptake than normal cells.Based on this,this paper plans to design and synthesize a glucose-bound NIR-Ⅱ small molecule fluorescent probe,which utilizes the excessive glucose uptake of leukemia cells to achieve targeted diagnosis and treatment of acute myeloid leukemia.This paper designed and synthesized NIR-Ⅱ fluorescent probe H4-PEG-Glu combined with water-soluble glucose,systematically studied the diagnostic and therapeutic application of H4-PEG-Glu at the cellular level,and initially explored at the animal level on the application of AML diagnosis.First,the NIR-Ⅱ fluorescent probe H4 and glucose were coupled by polyethylene glycol,and then their chemical properties,optical properties,and photothermal properties were characterized.The results show that H4-PEG-Glu is soluble in water,with a maximum emission wavelength of 1085 nm and a quantum efficiency of 1.38%(DCM).It has high chemical stability when irradiated with 808 nm laser for 1 hour in the aqueous phase.The photothermal effect is significant.Then,H4-PEG-Glu showed good biocompatibility.At a concentration of 20 μM,the survival rate of normal cells 293 T and hFOB1.19 were both greater than 80%.At the level of leukemia cells,H4-PEGGlu at a concentration of 20 μM enables targeted imaging of AML cells.At the animal level of the AML PDX model,after injecting H4-PEG-Glu(0.2 mL,5 mg / kg)into the tail vein for 6 hours,NIR-Ⅱ in vivo fluorescence imaging of AML was achieved under 3.5 W laser.In summary,this paper designed and synthesized a glucose-bound NIR-Ⅱ fluorescent probe H4-PEG-Glu,which has good biocompatibility,good optical properties and photothermal properties.At the cellular level,it showed good targeted fluorescence imaging and photothermal therapy for AML cells,and at the animal level,it initially showed the NIR-Ⅱ in vivo imaging diagnosis of AML.According to the existing research results of this paper,the follow-up can continue to study the effect of H4-PEG-Glu on AML mouse in vivo photothermal therapy,and further explore the application of this drug in the diagnosis and treatment of AML.