The Applications Of Polymeric Oxygen Sensors In Dissolved Oxygen Sensing And Imaging

Hypoxia usually leads to diseases,so dissolved oxygen sensing is essential for the diagnosis and treatment of certain diseases.Based on the optical analysis,we prepared some amphiphilic polymers and used them to encapsulate the hydrophobic oxygen probes platinum tetrakis?pentafluorophenyl?porphyrin?PtTFPP?to form oxygen sensitive micelles for biological dissolved oxygen sensing.Firstly,five kinds of four-arm amphiphilic polymers with different structures were synthesized through Atom Transfer Radical Polymerization?ATRP?to investigate the relationship of polymer structure and micelle property.As a result,longer hydrophobic chain resulted in smaller size,lower encapsulation efficiency and bigger Critical Micelles Concentrations?CMC?.Besides,the oxygen sensitivity,quantum yield and phosphorescence lifetime of fluorine-containing micelles were significantly better than those micells without fluorine.Specifically,the hypoxic phosphorescence lifetime of M3was 76?s,which was longer than any other reported PtTFPP micelles.Secondly,one micelle solution with the best oxygen-sensing performance was selected to achieve the extracellular oxygen-sensing during the respiration of Escherichia coli?E.Coli?and mouse macrophages.The results showed that the time to achieve hypoxia condition was shorter when cell density was higher.By using the Stern-Vlomer equation,we converted the phosphorescence intensity into dissolved oxygen concentration.Zebrafishes were introduced to achieve the real-time respiratory detection.This thesis also successfully extended the application of oxygen sensing micelles to intratumoral imaging of tumor-bearing mice.The phosphorescence intensity in tumor was1.6 times larger than that in the subcutaneous site,which means the oxygen sensing micelles are promising for in vivo tumor diagnosis.Finally,a new oxygen sensor with oxygen-insensitive naphthalimide-derived fluorophore and cell-penetrating peptide cRGD was prepared to achieve the intracellular oxygen sensing and imaging.The Fluorescence Resonance Energy Transfer?FRET?efficiency of reference fluorophore was 88%in the presence of PtTFPP,and the reference probe improved the detection accuracy of oxygen sensing.The results of flow cytometer and confocal imaging showed that cRGD can greatly increase the uptake of micelles by U87MG cells with high expression of integrin?_v?₃ to achieve targeted intracellular imaging.