Construction Of Dual-wavelength And Multi-scale In Vivo Monitoring System For Nano-drug Based On Fluorescence

Optical microimaging technology has become an important means to study the transport characteristics of nanodrugs due to its unique advantages of high-resolution imaging.However,at present,there are still some limitations to the simultaneous monitoring of nano-drugs in the deep blood,tissues and cells of living animals.In this thesis,a set of dual-wavelength(nano-carrier fluorescence signal,packaged drug fluorescence signal)multi-scale(macro,mesoscopic,micro)real-time fluorescence monitoring system is established to meet the needs of pre-clinical basic research and drugability evaluation of nano-drugs.Transport and release characteristics of nano-drugs at different levels in living small animals(average intravascular concentration,accumulation and damage in major metabolic organs,and intracellular effects in target cells).The dual-wavelength multi-scale fluorescence monitoring system built by this institute can more intuitively observe the dynamic changes of nano-medicines in the blood,more accurately monitor the metabolic behavior of nano-medicines,and truly and systematically reveal the nano-medicines in animals.The transport mechanism provides technical support.The main work content and innovations of the paper are as follows:1.Design the system technical scheme and build the system optical path hardware to meet the requirements of dual-wavelength multi-scale fluorescence monitoring.The system hardware includes three fiber bundles with different resolutions,four optical path modules,and an animal experiment platform.Through three fiber bundles with different resolutions,the in vivo fluorescence macro intensity monitoring,in vivo fluorescence mesoscopic imaging,and in vivo fluorescence micro imaging are effectively implemented Combined.The four optical path modules include laser fusion and spectroscopic optical paths,blood concentration monitoring optical paths,tissue imaging optical paths,and target cell imaging optical paths.2.Design and complete the system software function module and control platform.Design dual-wavelength multi-scale acquisition timing,and formulate hardware action timing to achieve dual-wavelength multi-scale real-time monitoring of nano-drug metabolism and release.Based on Labwindows and Matlab,a set of system upper computer software was developed to control the optical shutter,spectrometer,EMCCD,filter conversion wheel,and "Scan Image" software according to the time sequence.Software functions include parameter setting,human-computer interaction,data acquisition,data saving,etc.3.Design and verify the performance index of the test system.According to the different performance requirements of the three scales of the system,the corresponding validation experiments are designed respectively.The experimental results show that: all the indicators of the system meet the needs of multi-scale monitoring of nanodrugs in vivo;the system can monitor the metabolism and release characteristics of nanodrugs in small animals in real time.The dual-wavelength,multi-scale in-vivo monitoring system based on fluorescent nano-drugs can lay the foundation for in-vivo monitoring of nano-drugs and provide favorable conditions for further in-depth study of pre-clinical pharmacokinetics of nano-drugs.