熒光碳納米粒子的制備及應用研究
發(fā)布時間：2018-08-24 10:24
【摘要】：熒光碳納米粒子具有激發(fā)波長依賴性、優(yōu)良的發(fā)光效率、強的光耐受性等優(yōu)異的光學性質,受到研究者的廣泛關注。與傳統(tǒng)的半導體量子點相比,碳納米粒子具有較低的細胞毒性和良好的生物相容性,是可替代半導體量子點的最佳選擇。本論文采用不同方法制備了熒光碳納米粒子,對各種碳納米粒子的光學性質進行表征,并將所制備的碳納米粒子用于金屬離子檢測和生物成像。主要內(nèi)容包括：第一章：概述碳納米粒子組成、結構及發(fā)光特性,在此基礎上,進一步對碳納米粒子的制備方法及研究進展做了綜述。第二章：以殼聚糖(chitosan)為碳源,醋酸為冷凝劑,乙二胺(NAC)為氮摻雜劑,利用微波法快速簡單合成藍色熒光(λkcm=421 nm)氮摻雜碳量子點(N-CDs)。利用元素分析、透射電子顯微鏡(TEM)、高分辨率透射電子顯微鏡(HRTEM)、傅里葉變換紅外光譜(FTIR)、拉曼光譜(Raman spectroscopy)、X射線衍射(XRD)、X射線光電子能譜(XPS)、紫外可見吸收和熒光光譜對N-CDs進行了表征。研究表明,經(jīng)過氮摻雜后碳量子點的熒光量子產(chǎn)率高達20.1%,與未摻雜CDs的熒光量子產(chǎn)率相比,提高近三倍；Fe3+與N-CDs發(fā)生光電子轉移,可強烈地猝滅N-CDs的熒光,Fe3+檢測線性范圍為0.050-1.8 ppm,檢出限為10 ppb。N-CDs探針應用于人腎癌細胞成像和細胞中Fe3+檢測。第三章：以南瓜(pumpkin)為碳源,利用強酸(濃磷酸)氧化法制備了磷氮共摻雜黃色熒光碳量子點(R,N-CDs)、制備的P,N-CDs大小均一,平均尺寸為3.75 nm,表面富含磷酸基和酰胺鍵,熒光量子產(chǎn)率較高(9.42%),具有激發(fā)波長依賴性,熒光可逆性好。P,N-CDs具有pH值依賴性,當pH從1.5變化到7.4時,P,N-CDs位于550 nm處發(fā)射峰逐漸增強。在pH 4.7-7.4范圍內(nèi),P,N-CDs熒光強度與pH呈線性關系,酸度系數(shù)(pKa)為4.17。P,N-CDs具有很好的生物相容性和細胞膜穿透性,應用于人乳腺癌細胞內(nèi)pH檢測和斑馬魚活體成像,可有效避免生物體內(nèi)背景熒光的影響。第四章：采用五氧化二磷遇水放熱的性質將冰醋酸碳化,制得交聯(lián)狀空心熒光碳納米粒子(HC-NP)。所合成的碳納米粒子是一種復雜的混合物,能發(fā)出明亮的綠色熒光(λcm=498 nm),在紫外線輻照或長期貯存表現(xiàn)出良好的穩(wěn)定性。將其通過反相高效液相色譜法分離,得到13種不同粒徑的碳納米粒子組分。這些組分可產(chǎn)生不同顏色的熒光發(fā)射且呈現(xiàn)不同的量子產(chǎn)率,尤其我們分離得到了發(fā)紅色熒光的碳納米粒子。利用基質輔助激光解吸離子化飛行時間質譜(MALDI-TOF MS)對13種HC-NP組分進行解析,可顯示它們的碎片離子特性。分離后的組分與混合HC-NP相比,其細胞相容性更好,更適合做細胞成像的標記物。此外,選擇包括紅色熒光在內(nèi)的4種組分應用于人乳腺癌細胞共聚焦熒光顯微成像,顯示分離后的HC-NP僅穿透細胞膜進入細胞質。第五章：采用乙二胺(EDA)和濃磷酸(H3P04)中和放熱的性質將葡萄糖(glucose)碳化,制備了磷氮雙摻雜空心熒光碳點(PNHCDs)。該反應具有無需外部熱處理、儀器簡單和反應時間短等特點。制備的PNHCDs具有小的粒徑,空心結構,表面富含磷酸基、羥基、吡啶氮、吡咯氮等官能團。制備的PNHCDs用作抗癌藥物載體。以阿霉素(DOX)為模型藥物,測試了PNHCDs的載藥能力,載藥量高達35.43 wt%。DOX從PNHCDs-DOX中釋放具有pH可控性,在癌細胞中靶向釋放。PNHCDs-DOX用于模型鼠腫瘤治療,與DOX相比表現(xiàn)出更好的腫瘤抑制效應和更低的生物毒副作用,歸因于PNHCDs-DOX可加快體外細胞核轉運和增強體內(nèi)腫瘤累積效應。
[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.
【學位授予單位】：山西大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：TQ127.11;TB383.1
本文編號：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.
【學位授予單位】：山西大學
【學位級別】：博士
【學位授予年份】：2016
【分類號】：TQ127.11;TB383.1
【參考文獻】
相關期刊論文 前1條
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
，本文編號：2200525
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