荧光碳纳米粒子的制备及应用研究
发布时间：2018-08-24 10:24
【摘要】：荧光碳纳米粒子具有激发波长依赖性、优良的发光效率、强的光耐受性等优异的光学性质,受到研究者的广泛关注。与传统的半导体量子点相比,碳纳米粒子具有较低的细胞毒性和良好的生物相容性,是可替代半导体量子点的最佳选择。本论文采用不同方法制备了荧光碳纳米粒子,对各种碳纳米粒子的光学性质进行表征,并将所制备的碳纳米粒子用于金属离子检测和生物成像。主要内容包括：第一章：概述碳纳米粒子组成、结构及发光特性,在此基础上,进一步对碳纳米粒子的制备方法及研究进展做了综述。第二章：以壳聚糖(chitosan)为碳源,醋酸为冷凝剂,乙二胺(NAC)为氮掺杂剂,利用微波法快速简单合成蓝色荧光(λkcm=421 nm)氮掺杂碳量子点(N-CDs)。利用元素分析、透射电子显微镜(TEM)、高分辨率透射电子显微镜(HRTEM)、傅里叶变换红外光谱(FTIR)、拉曼光谱(Raman spectroscopy)、X射线衍射(XRD)、X射线光电子能谱(XPS)、紫外可见吸收和荧光光谱对N-CDs进行了表征。研究表明,经过氮掺杂后碳量子点的荧光量子产率高达20.1%,与未掺杂CDs的荧光量子产率相比,提高近三倍；Fe3+与N-CDs发生光电子转移,可强烈地猝灭N-CDs的荧光,Fe3+检测线性范围为0.050-1.8 ppm,检出限为10 ppb。N-CDs探针应用于人肾癌细胞成像和细胞中Fe3+检测。第三章：以南瓜(pumpkin)为碳源,利用强酸(浓磷酸)氧化法制备了磷氮共掺杂黄色荧光碳量子点(R,N-CDs)、制备的P,N-CDs大小均一,平均尺寸为3.75 nm,表面富含磷酸基和酰胺键,荧光量子产率较高(9.42%),具有激发波长依赖性,荧光可逆性好。P,N-CDs具有pH值依赖性,当pH从1.5变化到7.4时,P,N-CDs位于550 nm处发射峰逐渐增强。在pH 4.7-7.4范围内,P,N-CDs荧光强度与pH呈线性关系,酸度系数(pKa)为4.17。P,N-CDs具有很好的生物相容性和细胞膜穿透性,应用于人乳腺癌细胞内pH检测和斑马鱼活体成像,可有效避免生物体内背景荧光的影响。第四章：采用五氧化二磷遇水放热的性质将冰醋酸碳化,制得交联状空心荧光碳纳米粒子(HC-NP)。所合成的碳纳米粒子是一种复杂的混合物,能发出明亮的绿色荧光(λcm=498 nm),在紫外线辐照或长期贮存表现出良好的稳定性。将其通过反相高效液相色谱法分离,得到13种不同粒径的碳纳米粒子组分。这些组分可产生不同颜色的荧光发射且呈现不同的量子产率,尤其我们分离得到了发红色荧光的碳纳米粒子。利用基质辅助激光解吸离子化飞行时间质谱(MALDI-TOF MS)对13种HC-NP组分进行解析,可显示它们的碎片离子特性。分离后的组分与混合HC-NP相比,其细胞相容性更好,更适合做细胞成像的标记物。此外,选择包括红色荧光在内的4种组分应用于人乳腺癌细胞共聚焦荧光显微成像,显示分离后的HC-NP仅穿透细胞膜进入细胞质。第五章：采用乙二胺(EDA)和浓磷酸(H3P04)中和放热的性质将葡萄糖(glucose)碳化,制备了磷氮双掺杂空心荧光碳点(PNHCDs)。该反应具有无需外部热处理、仪器简单和反应时间短等特点。制备的PNHCDs具有小的粒径,空心结构,表面富含磷酸基、羟基、吡啶氮、吡咯氮等官能团。制备的PNHCDs用作抗癌药物载体。以阿霉素(DOX)为模型药物,测试了PNHCDs的载药能力,载药量高达35.43 wt%。DOX从PNHCDs-DOX中释放具有pH可控性,在癌细胞中靶向释放。PNHCDs-DOX用于模型鼠肿瘤治疗,与DOX相比表现出更好的肿瘤抑制效应和更低的生物毒副作用,归因于PNHCDs-DOX可加快体外细胞核转运和增强体内肿瘤累积效应。
[Abstract]:Fluorescent carbon nanoparticles have attracted much attention due to their excellent optical properties, such as excitation wavelength dependence, excellent luminous efficiency, strong light tolerance and so on. Compared with traditional semiconductor quantum dots, carbon nanoparticles have lower cytotoxicity and good biocompatibility, and are the best alternative to semiconductor quantum dots. In this paper, fluorescent carbon nanoparticles were prepared by different methods to characterize the optical properties of various carbon nanoparticles, and the prepared carbon nanoparticles were used for metal ion detection and bioimaging. The preparation methods and research progress of nanoparticles are reviewed. Chapter 2: Blue fluorescence (lambda KCM = 421 nm) N-doped carbon quantum dots (N-CDs) were synthesized by microwave irradiation using chitosan as carbon source, acetic acid as condenser and ethylenediamine (NAC) as nitrogen dopant. Element analysis, transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRPT) were used. The N-CDs were characterized by emission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible absorption and fluorescence spectroscopy. The results showed that the fluorescence quantum yield of N-doped carbon quantum dots was as high as 20.1%, which was compared with that of undoped CDs. Quantum yield was nearly three times higher than that of the control group. Photoelectron transfer between Fe3+ and N-CDs strongly quenched the fluorescence of N-CDs. The linear range of Fe3+ detection was 0.050-1.8 ppm. The detection limit was 10 ppb. Yellow phosphorus-nitrogen co-doped fluorescent carbon quantum dots (R, N-CDs) were prepared. The size of P, N-CDs was uniform, the average size was 3.75 nm, the surface was rich in phosphoric acid and amide bonds, the fluorescence quantum yield was high (9.42%), the excitation wavelength was dependent, the fluorescence reversibility was good. P, N-CDs had pH dependence. When the pH changed from 1.5 to 7.4, P, N-CDs was located at 550 nm. In the range of pH 4.7-7.4, the fluorescence intensity of P and N-CDs showed a linear relationship with pH, and the acidity coefficient (pKa) was 4.17.P. N-CDs had good biocompatibility and cell membrane penetration. It can be used to detect intracellular pH of human breast cancer cells and imaging zebrafish in vivo, which can effectively avoid the influence of background fluorescence. Crosslinked hollow fluorescent carbon nanoparticles (HC-NP) were prepared by carbonizing glacial acetic acid with phosphorus pentoxide in the presence of exothermic water. The carbon nanoparticles synthesized are a complex mixture that emits bright green fluorescence (lambda cm = 498 nm) and exhibit good stability under ultraviolet irradiation or long-term storage. Thirteen components of carbon nanoparticles with different sizes were obtained by chromatographic separation. These components can emit fluorescence with different colors and exhibit different quantum yields. In particular, red fluorescent carbon nanoparticles were separated. Thirteen HC-NP components were introduced by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition, four components including red fluorescence were selected for confocal fluorescence microscopy of human breast cancer cells, showing that the separated HC-NP only penetrated the cell membrane. Chapter 5: Glucose (glucose) was carbonized by neutralization and exothermic properties of EDA and H3P04 to prepare phosphorus-nitrogen double-doped hollow fluorescent carbon dots (PNHCDs). PNHCDs were prepared and used as anticancer drug carriers. Doxorubicin (DOX) was used as a model drug to test the drug-loading capacity of PNHCDs. The drug-loading capacity of PNHCDs was up to 35.43 wt%. The release of DOX from PNHCDs-DOX was pH-controlled and targeted in cancer cells. PNHCDs-DOX can accelerate nuclear transport in vitro and enhance tumor accumulation in vivo, which is attributed to better tumor inhibition and lower biological toxicity than PNHCDs-DOX.
【学位授予单位】：山西大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TQ127.11;TB383.1
本文编号：2200525
[Abstract]:Fluorescent carbon nanoparticles have attracted much attention due to their excellent optical properties, such as excitation wavelength dependence, excellent luminous efficiency, strong light tolerance and so on. Compared with traditional semiconductor quantum dots, carbon nanoparticles have lower cytotoxicity and good biocompatibility, and are the best alternative to semiconductor quantum dots. In this paper, fluorescent carbon nanoparticles were prepared by different methods to characterize the optical properties of various carbon nanoparticles, and the prepared carbon nanoparticles were used for metal ion detection and bioimaging. The preparation methods and research progress of nanoparticles are reviewed. Chapter 2: Blue fluorescence (lambda KCM = 421 nm) N-doped carbon quantum dots (N-CDs) were synthesized by microwave irradiation using chitosan as carbon source, acetic acid as condenser and ethylenediamine (NAC) as nitrogen dopant. Element analysis, transmission electron microscopy (TEM) and high resolution transmission electron microscopy (HRPT) were used. The N-CDs were characterized by emission electron microscopy (HRTEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), ultraviolet-visible absorption and fluorescence spectroscopy. The results showed that the fluorescence quantum yield of N-doped carbon quantum dots was as high as 20.1%, which was compared with that of undoped CDs. Quantum yield was nearly three times higher than that of the control group. Photoelectron transfer between Fe3+ and N-CDs strongly quenched the fluorescence of N-CDs. The linear range of Fe3+ detection was 0.050-1.8 ppm. The detection limit was 10 ppb. Yellow phosphorus-nitrogen co-doped fluorescent carbon quantum dots (R, N-CDs) were prepared. The size of P, N-CDs was uniform, the average size was 3.75 nm, the surface was rich in phosphoric acid and amide bonds, the fluorescence quantum yield was high (9.42%), the excitation wavelength was dependent, the fluorescence reversibility was good. P, N-CDs had pH dependence. When the pH changed from 1.5 to 7.4, P, N-CDs was located at 550 nm. In the range of pH 4.7-7.4, the fluorescence intensity of P and N-CDs showed a linear relationship with pH, and the acidity coefficient (pKa) was 4.17.P. N-CDs had good biocompatibility and cell membrane penetration. It can be used to detect intracellular pH of human breast cancer cells and imaging zebrafish in vivo, which can effectively avoid the influence of background fluorescence. Crosslinked hollow fluorescent carbon nanoparticles (HC-NP) were prepared by carbonizing glacial acetic acid with phosphorus pentoxide in the presence of exothermic water. The carbon nanoparticles synthesized are a complex mixture that emits bright green fluorescence (lambda cm = 498 nm) and exhibit good stability under ultraviolet irradiation or long-term storage. Thirteen components of carbon nanoparticles with different sizes were obtained by chromatographic separation. These components can emit fluorescence with different colors and exhibit different quantum yields. In particular, red fluorescent carbon nanoparticles were separated. Thirteen HC-NP components were introduced by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). In addition, four components including red fluorescence were selected for confocal fluorescence microscopy of human breast cancer cells, showing that the separated HC-NP only penetrated the cell membrane. Chapter 5: Glucose (glucose) was carbonized by neutralization and exothermic properties of EDA and H3P04 to prepare phosphorus-nitrogen double-doped hollow fluorescent carbon dots (PNHCDs). PNHCDs were prepared and used as anticancer drug carriers. Doxorubicin (DOX) was used as a model drug to test the drug-loading capacity of PNHCDs. The drug-loading capacity of PNHCDs was up to 35.43 wt%. The release of DOX from PNHCDs-DOX was pH-controlled and targeted in cancer cells. PNHCDs-DOX can accelerate nuclear transport in vitro and enhance tumor accumulation in vivo, which is attributed to better tumor inhibition and lower biological toxicity than PNHCDs-DOX.
【学位授予单位】：山西大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：TQ127.11;TB383.1
【参考文献】
相关期刊论文 前1条
1 Mohamed A Fahim;Hazem Kataya;Rkia El-Kharrag;Dena AM Amer;Basel al-Ramadi;Sherif M Karam;;Ghrelin attenuates gastrointestinal epithelial damage induced by doxorubicin[J];World Journal of Gastroenterology;2011年33期
，本文编号：2200525
本文链接：https://www.wllwen.com/kejilunwen/huaxuehuagong/2200525.html
