Novel Upconversion Fluorescent Nano Contrast Agent For Intelligent Ratiometric Fluorescence Imaging Of Hypoxic Cells

Cancer is still one of the difficult problems that plague human life and health,with millions of lives lost every year due to cancer.With the continuous technological advances in nanotechnology in recent years,the intersection of nanotechnology and pharmaceuticals has received widespread attention.Based on the advantages of low toxicity and stable properties of nanomedicine,the use of nanoparticles for the treatment of tumor tissue has become an important direction in the field of biomedical science.Compared with normal tissues,the TME(tumor microenvironment)has some characteristics such as high concentrations of hydrogen peroxide and glutathione,cellular hypoxia,and acidic p H.In this study,a upconversion ratio fluorescent nano contrast agent for detecting the hypoxia characteristic in tumor tissue was designed and synthesized for effective monitoring of cancer lesions in the human body.The contrast agent was self-assembled by using an azobenzene-modified four-fluorinated yttrium sodium upconversion nanoparticle as the substrate and β-cyclodextrin-modified gold nanoparticles through host-guest interactions.Under normal oxygen conditions,fluorescence resonance energy transfer(FRET)occurs between the upconversion nanoparticle and the gold nanoparticle,resulting in the quenching of green emission light and no effect on red light.When the upconversion fluorescent nano contrast agent is in a hypoxic environment,the azobenzene bond is reduced and broken down by the action of hepatic microsomal enzymes,causing the material to undergo disassembly and no longer maintaining the FRET phenomenon,thus resulting in the recovery of green fluorescence,and achieving proportional fluorescence imaging of tumor tissues in vivo.Compared with traditional downconversion contrast agent,this upconversion fluorescent nano contrast agent has low background fluorescence and good photostability,and the 980 nm excitation penetration in the near-infrared region is strong;the use of azobenzene as a response group is less affected by biological interference,and is not affected by the reducing microenvironment of acidity and thiol groups;compared with traditional FRET fluorescent contrast agent,the energy absorption capacity of gold nanoparticles is stronger and the signal change is more sensitive,with high signal-to-noise ratio of proportional fluorescence.The contrast agent not only responds to hypoxic environments in vitro,but also exhibits good biocompatibility and successfully distinguishes between normal oxygen and hypoxic states of cells.