The Synthesis And Research Of High Stability Block Copolymer Fluorescein Nanoparticle Probe

Fluorescent molecular imaging technology has attracted considerable attention in the field of disease diagnosis due to its advantages such as low price,simplicity of operator,high sensitivity,and good repeatability.In particular,Near-infrared fluorescence guided cancer surgery has become a real-time image guiding method in tumor surgery.Fluorescent probe,as the key component of fluorescence imaging technology,is undoubtedly the decisive factor affecting the clarity and resolution of fluorescent imaging.An excellent fluorescent probe for fluorescent imaging needs to have a suitable wavelength,high quantum yield,and great photostability,good biocompatibility and other advantages.In tumor surgery,long-term real-time tracking imaging of the tumor tissue area is required,meaning that the fluorescent probe needs to be exposed to high-intensity excitation light for a long time without interruption,which makes high demands for the photostability of the fluorescent probe.So far,while organic small molecule fluorescent dyes and their derivatives are still the most commonly used fluorescent probes,most of them are often suffering from their poor photostability,which limits their use in more in-depth applications.In this paper,the fluorescent imaging dye fluorescein,which was approved by both FDA and CFDA,was selected to explore a method that can effectively improve the photostability of small molecule fluorescent probes.The block copolymer nano-system is a new type of nano-system developed at the end of the last century.It has a very wide range of applications in the fields of chemical detection,drug delivery,and tumor therapy.Through the assembly of amphiphilic block copolymers such as PEG-PCL and POX into nanoparticles in the aqueous phase,the load can be wrapped in the core of the nanoparticles,and then the enhanced permeability and retention(EPR)effect of the solid tumor can be used to achieve the passive targeting of tumor tissue.In the second chapter of this paper,aiming at the defect of poor photostability of small molecule fluorescent probes,a method for improving the photostability of fluorescein probes by using amphiphilic block copolymers to coat fluorescein to form nanostructures was proposed,and the effects of two different block copolymers(PEG-PCL and POX)on the photostability of fluorescein were investigated.The results showed that the two different block copolymers of PEG-PCL and POX could be assembled into uniform and stable spherical nanoparticles in the aqueous phase.After carrying fluorescein,the size of the nanoparticles was about 50 nm.Both of them could improve the photostability of small molecule fluorescein and increase the half-life of the fluorescein photooxidation reaction by several times.This study also showed that this pure physical coating had its own limitations,the self-quenching of fluorescein in the core of the nanoparticles,which results in a very low fluorescence quantum yield of the nanoprobe.At present,there are three main methods for improving the light stability of small molecule fluorescent probes: chemical modification to form derivatives;structural modification to coat the reactive sites with specific structures;and formation of nanostructures.The second chapter of this paper explored the effect of block copolymer nanostructures on the photostability of small molecule fluorescein.While the third chapter combined the latter two methods,using a specific structure(PCL nano-insulating layer)to coat small fluorescein molecules.The PCL-coated fluorescein,was then assembled with the block copolymer into a nanostructure to improve the fluorescence quantum yield and photostability.The third chapter mainly explored the relationship between the quantum yield,photostability of the nanoprobe and the coating thickness of PCL nano-insulation layer.The results showed that after coating the fluorescein with the PCL nano-insulating layer,the fluorescence quantum yield of the nanoprobe was greatly improved,even could reach 0.75.This method successfully solved the self-quenching and low quantum yield of the block copolymer fluorescein nanoprobe.In addition,the photostability of the nanoprobe had also been improved to a large extent.The half-life of nanoparticles with extremely high thickness of the nano-insulating layer coating could be 30 times longer than the uncoated nanoparticles and 60 times longer than the small molecule fluorescein.