Synthesis And Bioimaging Of Biodegradable Fluorescent Nanoparticles With Aggregation-Induced Emission Characteristics

Fluorescence imaging has the characteristics of high sensitivity,space and time resolution,and is widely used in the monitoring of active substances in vivo,disease diagnosis and biological activity detection.Constructing fluorescence probes with high sensitivity and high signal-to-noise ratio is of great significance for fluorescence imaging.The diversity and biodegradability of organic dyes make fluorescent organic probes attracted more and more attentions.Besides,fluorescent organic probes have the advantages of diversity synthesis,easy surface function and low toxicity.Fluorescent organic nanoparticles prepared from organic emitters as fluorescence cores and biocompatible/degradable polymers as encapsulated substrates have developed into a new generation of probes and applied to in vivo bioimaging.Due to the aggregation caused quenching（ACQ）effect of traditional organic dyes,their biological imaging and tracking applications under physiological conditions are severely limited.Since the first discovery of aggregation induced emission（AIE）in 2001,polymeric fluorescent nanoparticles based on AIE dyes provide new avenue for the preparation of desired probes.To solve the ACQ effect and the difficult biodegradability of AIE probe,this paper puts forward the research idea of constructing biodegradable AIE fluorescence nanoprobe.The main contents of this thesis can be classified as the following four parts:In chapter 1,we introduce the advantages of the fluorescence organic nanoprobe and the problems of fluorescence quenching of conventional dyes in high concentration,and leads to the concept of AIE.The recent advances of AIE dyes in biological imaging,biosensor and tumor therapy are summarized,and the applications of degradable polymers in biomedicine are emphatically discussed.The idea of designing biodegradable fluorescent probes with AIE properties is presented.In chapter 2,we fabricate the fluorescent nanoparticles using Ad-modified AIE-active dye as the core,and the hydrophilicβ-CD dimer as encapsulation matrix through host-guest interaction between Ad andβ-CD.The obtained Ph-Ad/β-CD FONs show uniform size distribution,high water dispersity,desirable optical properties and biocompatibility.By virtue of its simplification and high efficiency as the bioimaging nanoprobe,further development of AIEgens with longer emission will facilitate the development of desired probes for in vivo imaging.In chapter 3,BPA is prepared by the condensation of 2,4-dihydroxybenzophenone with hydrazine hydrate.Biodegradable BPA-PEG₂₀₀₀ PUs are synthesized by two-step polymerization.Fluorescence probes are constructed of BPA and biocompatible PEG segment as encapsulation matrix.Cell viability evaluations proved that BPA-PEG₂₀₀₀FONs had good biocompatibility.Besides,the utilization of FONs in biomedical applications was studied in cell imaging.In chapter 4,the side chain modified amino acid was prepared by thiol-ene click reaction between Phe-Am and Cys,and then transformed into polymerizable AIE-active monomers.The amino groups in the PEG segment were used to initiate the ROP of Cys-Phe NCA monomer to fabricate biodegradable FONs with high water dispersity.These excellent properties generate the great potential of FONs in bioimaging applications.