胡珺,杨畅,陈思颖,赵青,王永林
HU Jun,YANG Chang,CHEN Siying,ZHAO Qing,WANG Yonglin

• 1:贵州医科大学药学院
• 2:贵州医科大学贵州省药物制剂重点实验室
• 3:贵州医科大学民族药与中药开发应用教育部工程研究中心

摘要(Abstract)：

目的:制备荧光量子点和叶酸偶联荧光量子点脂质体纳米探针,初步确证探针的性质,为相关肿瘤的早期荧光诊断奠定基础。方法:采用水相合成法合成3-巯基丙酸修饰的水溶性CdTe量子点,将脂质材料与叶酸分子连接,通过薄膜水化法制备得到叶酸偶联的荧光量子点脂质体纳米探针,利用紫外可见吸收光谱(UVvis)、红外光谱(IR)、分子荧光光谱法(MFS)、核磁共振(NMR)等方法确证荧光量子点、叶酸偶联脂质材料、叶酸偶联荧光量子点脂质体纳米探针性质;于-4℃冰箱内贮存6个月,观察叶酸偶联荧光量子点脂质体纳米探针的稳定性。结果:荧光量子点的荧光性质可随着反应时间的变化而变化,红外光谱、紫外可见吸收光谱、核磁共振氢谱证实叶酸偶联脂质材料合成成功;合成得到的叶酸偶联荧光量子点脂质体纳米探针平均粒径为462.9 nm,zeta电位为-0.072 2 mV,在520 nm处有最大荧光发射峰;放置6个月后,荧光性质未见明显变化。结论:叶酸偶联脂质体成功将CdTe量子点包裹,制备得到荧光强度高、性质稳定的纳米探针。
Objective: To prepare fluorescence quantum dots and folate-conjugated quantum dots liposome nanoprobes for the molecular fluorescence diagnosis of early tumors,and to characterize their properties preliminarily. Methods: Water-soluble Cd Te quantum dots modified with 3-mercaptopropionic acid was synthesized in water. Lipid material was linked with folic acid,and folate-conjugated fluorescent quantum dots liposome nanoprobes were prepared by thin membrane hydration method. UV-vis spectra,IR spectra,MFS and NMR detection methods were used to characterize the quantum dots,folate-conjugated lipid materials,and folate-conjugated quantum dots liposomes nanoprobe. The stability of folate-conjugated quantum dots liposomes nanoprobe was observed after stored in-4 ℃ for 6months. Results: The Fluorescence properties of QDs changed with the reaction time. The success of synthesis of folate-conjugated liposomes was proved by UV-vis spectra,IR spectra,MFS and NMR detection methods. The average diameter of folate-conjugated quantum dots liposome nanoprobes was462. 9 nm,and zeta potential was-0. 072 2. The maximum fluorescence emission peak was located at520 nm,and the fluorescence did not change after 6 month storage. Conclusion: Quantum dots were successfully entrapped in the folate-conjugated liposomes,and nanoprobes with strong and stable fluorescent have been successfully prepared.

关键词(KeyWords)： 叶酸;偶联;荧光量子点;脂质体;纳米探针
folic acid;conjugation;fluorescence quantum dots;liposomes;nanoprobes

Abstract:

Keywords:

基金项目(Foundation): 贵州省科学技术基金项目[黔科合J字(2014)2019号];; 贵州医科大学博士启动基金(院基金合同字第014号);; 贵州省卫生计生委科学技术基金项目(gzwjkj2015-1-027);; 贵州省科技厅-贵州医科大学科学技术联合基金项目[黔科合LH字(2016)7364号];; 贵州省教育厅现代药物研究开发协同创新中心[黔教合协同创新字(2013)04号]

作者(Author): 胡珺,杨畅,陈思颖,赵青,王永林
HU Jun,YANG Chang,CHEN Siying,ZHAO Qing,WANG Yonglin

DOI: 10.19367/j.cnki.1000-2707.2017.01.010

参考文献(References)：

• [1]Song EQ,Zhang ZL,Luo QY,et al.Tumor cell targeting using folate-conjugated fluorescent quantum dots and receptor-mediated endocytosis[J].Clinical Chemistry,2009(5):955-963.
• [2]Chang Y,Wei C,Brian QB,et al.Recent progress on the liposomes loaded with quantum dots[J].Nanoscience and Nanotechnology,2012(1):257-270.
• [3]那佳,侯明.Cd Te量子点的合成及作为离子荧光探针的应用[J].桂林理工大学学报,2010(1):133-136.
• [4]王显祥,杨中科,单志,等.大单室Cd Te量子点脂质体的制备及其体内代谢途径[J].中国科学,2010(10):1503-1508.
• [5]傅晓源,陈富韬,张浩伟,等.量子点在叶酸偶联白蛋白纳米粒偶联肿瘤细胞研究中的应用[J].中国现代医学杂志,2008(23):3418-3420.
• [6]华晓峰.量子点与生物分子的偶联及其应用[D].武汉:华中科技大学,2006.
• [7]Wafa T.AJamal,Khuloud T.Al-Jamal,Bowen Tian,et al.Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration[J].Molecular Pharmaceutics,2009(2):520-530.
• [8]黄英男,吴昊,沈锡中.叶酸受体在肿瘤偶联诊断和治疗中的应用[J].复旦学报:医学版,2012(1):74-79.
• [9]林章碧,苏星光,张皓,等.用水溶液中合成的量子点作为生物荧光标记物的研究[J].高等学校化学学报,2003(2):216-220.
• [10]汪梅花.叶酸偶联紫杉醇纳米脂质体的制备及其生物学效应的研究[D].苏州:苏州大学,2008.
• [11]安智娇.叶酸受体介导PH敏感型抗肿瘤药物偶联给药系统研究[D].北京:北京协和医科大学,2011.
• [12]Wu J,Liu Q,Lee RJ.A folate receptor-targeted liposomal formulation for paclitaxel[J].Int.J Pharm,2006(1-2):148-153.
• [13]纪桢.叶酸修饰的异土木香内酯长循环脂质体研究[D].西安:西北大学,2013.
• [14]Lee RJ,Low PS.Folate-mediated tumor cell targeting of liposome-entrapped doxorubicin in vitro[J].Biochim Biophys Acta,1995(2):134-144.
• [15]Yu WW,Qu LH,Peng XG,et al.Experimental determination of the extinction coefficient of Cd Te,Cd Se,and Cd S nanocrystals[J].Chem Mater,2003(14):2854-2860.

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