Preparation Of Novel Fluorescent Carbon Dots And Their Applications In Targeted Biological Imaging And Tumor Treatment

Objective:As a novel kind of nano-materials,carbon dots have been widely used in bio-medical field due to their excellent luminescence performance and good biocompatibility.Nowadays cancer has become a main threat to human beings.Prompt and effective treatment is vital for improving the survival of cancer patients.Traditional antitumor drugs bring serious side effects because they lack targeting ability.Therefore,developing new drug delivery platform is meaningful for the targeted treatment of cancer.The major work of this thesis is described as follows:1.Using citric acid and p-aminosalicylic acid as raw materials and absolute ethanol as a solvent,green fluorescent carbon dots?G-CDs?were synthesized by solvothermal method.G-CDs have been used in Fe³⁺detection.2.By loading NH₂-PEG-COOH,transferrin?Tf?,and doxorubicin hydrochloride?DOX?to G-CDs one by one,the nanocomposite CD-PEG-Tf@DOX was prepared.Then applications of CD-PEG-Tf@DOX in targeted imaging and tumor treatment effects have been studied.Methods:1.Using citric acid and p-aminosalicylic acid as raw materials and absolute ethanol as a solvent,green fluorescent carbon dots?G-CDs?were synthesized by solvothermal method.Then G-CDs were characterizd by transmission electron microscopy,atomic force microscope,X-ray diffraction,X-ray photoelectron spectroscopy,and Fourier transform infrared spectroscopy.UV-visible absorption spectra and fluorescence spectra were performed to study the optical properties of G-CDs.Effects of ionic strength,illumination time and pH on the stability of G-CDs were also investigated.At last,selectivity of G-CDs to metal ions was sdutied.2.The nanocomposite CD-PEG-Tf@DOX was constructed by using the prepared G-CDs as a carrier,loading NH₂-PEG-COOH,transferrin?Tf?and doxorubicin hydrochloride?DOX?.Fourier transform infrared spectrum,Zeta potential,UV-visible absorption spectra,and fluorescence spectra were measured to study the structural and optical properties of CD-PEG-Tf@DOX.Then,the uptake of CD-PEG-Tf@DOX by cells was investigated by confocal imaging and flow cytometry.And the lethality of CD-PEG-Tf@DOX to cells was studied by ovserving cell morphology,MTT assay,cell scratch method,AM/PI staining as well as flow cytometry.In order to evaluate the therapeutic performance of CD-PEG-Tf@DOX,tumor volume and weight was monitored.Besides,liver and kidney functions were tested.Tissue slice staining of main organs was also conducted.Results:1.The prepared G-CDs are nearly spherical with size of 2-8 nm.There are abundant carboxyl and amino groups on the surface.G-CDs exhibit high fluorescence quantum field?45%?,good water-solubility and optical stability.Besides,G-CDs display highly sensitive and selective fluorescence response to Fe³⁺,with a detection limit of 0.35?mol/L.2.The prepared nanocomposite,CD-PEG-Tf@DOX can form an effective energy resonance transfer?FRET?system,and it has a DOX loading rate of 16.5%.DOX can be released from CD-PEG-Tf@DOX effectively in the condition of pH 5.5.Under the action of Tf,CD-PEG-Tf@DOX can only enter into tumor cells?MCF-7?and release DOX.As a result,CD-PEG-Tf@DOX can only kill tumor cells efficiently.In vivo study reveals that CD-PEG-Tf@DOX has obvious inhibitory effect on tumor in nude mice,and has no effect on the main organs and can achieve highly efficient and low-toxic tumor targeted therapy.Conclusion:In this paper,simple green materials are used to synthesize carbon dots with high quantum yield,good water solubility and low toxicity.The carbon dots can be used not only for the selective detection of Fe³⁺,but also as a carrier to construct a nano-drug targeted delivery system.The drug-carrying platform constructed accordingly can be used for targeted cell imaging and tumor targeted therapy.And other fields have certain application prospects.