Construction Of Functional Fluorescent Polymer Systems Based On RAFT Polymerization And Cell Imaging Study

With the development of technology,functional materials play an extremely important role in various fields.Especially in the life science field,functional polymers are widely used for drug delivery,biosensing and fluorescence imaging.In order to obtain better application result,multi-functional polymers have made great progress.However,the cumbersome preparation methods,the complicated synthesic process and the rare types of hydrophilic polymers greatly limit the development of amphiphilic functional polymers.Therefore,how to design functional fluorescent polymers with simple structure and versatility and explore their application in life science is a difficult problem to be solved.In this paper,a series of novel amphiphilic functional fluorescent polymers were successfully synthesized by RAFT polymerization.Via endowing functionalization to hydrophilic segments,it not only enriched the types of tumor-targeting polymers,but also reduced the difficulty in constructing functional polymer systems,which provided a reference for further development of drug delivery and bioimaging.Moreover,the monochromatic fluorescent signals was made to realize the multi-response imaging for tumor cell microenvironment,and a class of polymer system was developed successfully,which greatly simplified the preparation of functional polymers,especially multi-functional polymer systems.It provided a new idea for further development of functional polymers with simple structure and rich functions.This paper was divided into three parts.The specific research contents and conclusions were summarized as follows:1.Construction of targeted fluorescent polymer system for cell imagingTargeted drug delivery and imaging have been one of the scientific challenges which researchers are eager to solve.However,expensive cost,single applicability,and complex synthetic routes have greatly limited the widespread use of most current targeting carriers.In this parper,a novel near-infrared fluorescent block polymer PMMA-b-P(GATH-co-BOD)was successfully synthesized by the reversible addition-fragmentation chain transfer polymerization(RAFT).The hydrophilic end of PGATH was a kind of new hydrophilic polymer based on glucose as polymerized units.It not only had hydrophilicity but also had the ability of targeting tumor cells.The amphiphilic polymer could self-assemble into spherical nanomicelles with 40 nm,and the maximum excitation and emission wavelengths of the nanomicelles were located in the near-infrared region,and had near-infrared fluorescence properties.The vitro cell experiments demonstrated that the amphiphilic polymer not only had very low cytotoxicity,but also had significant active targeting ability to tumor cells,and the active targeting ability was associated with the glucose transporter GLUT1.The system not only utilized a cheap and readily available,and biocompatible glucose molecules as polymer units to construct a novel hydrophilic polymer,but also endowed the function of target tumor cells to the amphiphilic polymer.This construction of the polymer system had a very broad application prospect in the fields of drug delivery and tumor diagnosis and treatment.2.Construction of multi-functional fluorescent polymer system for cell imagingDue to the difference of tumor tissue from normal physiological temperature,the thermo-responsive polymer systems have significant developmental value in drug delivery and bioimaging.However,single-function polymer systems often worked via a single response,which was subject to many limitations.The construction of a double or multi-functional polymer system could give the polymer more stimulating responsiveness,and could also make these functions worked synergistically,and exert greater application value.Combining the advantages of the functionalization of the hydrophilic segment in the previous chapter,and utilizing the characteristics of the microenvironmental responsiveness of tumor cells,in this parper,a new type of fluorescent block polymer PGATH-b-P(NIPAM-co-BOD)was successfully synthesized by RAFT polymerization,which had both temperature responsiveness and tumor targeting multiple functions.Fluorescence experiments shown that the polymer had temperature responsiveness in solution,which the fluorescence intensity gradually increases with the increase of system temperature,and had cyclic reversibility.The vitro cell experiments demonstrated that this polymer not only had very low cytotoxicity,but also reflected the characteristic of intracellular temperature responsiveness.Meanwhile,due to the presence of the hydrophilic end PGATH,the functional polymer exhibited the ability of targetting tumor cells.Due to its dual functions of temperature responsiveness and tumor targeting,the functional polymer system could greatly enhance the synergistic effect of multiple functions and expand its application value in drug delivery and bioimaging.3.Construction of dual-responsive fluorescent polymer system for cell imagingAlthough multi-functional polymers could exert better applications,complex and cumbersome synthetic steps,a single type of hydrophilic polymer,greatly limited the development of the polymer system in the field of drug delivery and tumor imaging.application.Meanwhile,for multi-functional fluorescent polymer systems,single-color fluorescent signals were difficult to achieve multiple responsive imaging,so the combination of multiple fluorescent molecules was required to achieve multiple-response imaging,which greatly increased difficultiy for constructing polymer systems.In this chapter,we had explored the multi-response imaging with monochromatic fluorescent signals for tumor cell microenvironment.A class of AIE-based temperature and pH duel-responsive polymer system was successfully synthesized by RAFT polymerization.By changing the response conditions(temperature and pH),one polymer chain could self-assemble to two spherical nanomicelles with opposite core/shell structures.Due to the different response positions of the fluorescent molecules TPE,this polymer system could achieve a good fluorescence response effect for temperature and pH in solutions and living cells...