近红外光响应纳米药物的化学制备及性能研究

发布时间：2018-07-05 15:54

本文选题：连续热注射法 + 近红外光敏药物　；参考：《合肥工业大学》2017年硕士论文

【摘要】：近红外光响应纳米药物的制备与应用是化学、生物、材料、医学等领域的研究热点。通过将上转换荧光材料与不同性质的材料合理地复合在一起,利用材料之间的协同效应,制备的纳米药物可以在纳米尺度范围内对肿瘤进行监控,分析以及治疗。但现有的合成近红外光响应的上转换荧光材料需要多次离心沉淀、水洗涤、重新分散晶种等一系列复杂操作。针对此问题,本论文发展了一种方便、低毒性的连续热注射法,此合成方法是在十八烯和油酸的混合溶液里加入的定量NH_4F和NaOH,将反应溶液升到高温后,间隔一定时间,逐次注射镧系离子的油酸复合物,在高温下成核生长,在反应体系的比表面能要求最小的情况下,快速生成上转换纳米晶体。利用此方法,我们制备了近红外光响应的纳米药物,具体如下:(1)通过连续热注射法,首先制备了超小的CaF_2:Yb,Er近红外光响应的荧光纳米颗粒(10 nm)。通过透射电子显微镜、X-射线衍射仪、X-射线能谱仪、荧光光谱仪、荧光光谱仪等表征手段,发现合成过程中Na~+的浓度能改善CaF_2:Yb,Er的结晶性、荧光强度和形貌,并发现连续热注射法能有效提高的上转换纳米颗粒的荧光强度,且可有效调控上转换纳米颗粒的尺寸大小,证明了连续热注射法是一种简单、高效、通用的合成上转换纳米颗粒的方法。(2)在连续热注射法基础上,通过层层自组装合成了近红外光敏药物NaYF_4:Yb,Tm@NaYF_4(UCNPs)@mSiO_2/CdS。通过透射电子显微镜发现所制备的UCNPs、CdS和介孔SiO_2的尺寸分别为50 nm、5 nm和10 nm。X-射线能谱仪和氮气吸附脱附等表征手段发现UCNPs@mSiO_2/CdS具有良好的结晶性和巨大的比表面积(760 m2g-1)。紫外可见光吸收光谱和荧光光谱发现UCNPs的上转换荧光(380、451和470 nm)被半导体CdS通过荧光能量共振转移过程淬灭。通过活性自由基探针对苯二甲酸发现在近红外光照射下,UCNPs会激发CdS产生羟基自由基(·OH)。光降解罗丹明B实验表明UCNPs@mSiO_2/CdS在近红外光具有高效的产生活性自由基的效率。同时,在980 nm近红外光照射下,将光敏药物UCNPs@mSiO_2/CdS与Hela癌细胞一起培养24 h,进行光动力治疗研究,实验结果表明所制备的光敏药物系统UCNPs@mSiO_2/CdS有良好光动力治疗效果。
[Abstract]:The preparation and application of NIR-responsive nanopharmaceuticals is a hotspot in chemistry, biology, materials, medicine and so on. By combining the up-conversion fluorescent materials with different materials reasonably, and utilizing the synergistic effect between the materials, the prepared nanopharmaceuticals can monitor, analyze and treat the tumors in the nanometer scale. However, the existing up-conversion fluorescent materials with near-infrared light response require a series of complex operations, such as centrifugation, water washing and re-dispersing of seeds. In order to solve this problem, a convenient and low toxicity continuous thermal injection method was developed in this paper. The synthetic method was to add quantitative NH _ 4F and NaOH in the mixed solution of octadecene and oleic acid, and to raise the reaction solution to high temperature at intervals of a certain time. The oleic acid complexes of lanthanide ions were injected one by one and nucleated at high temperature. Under the condition that the specific surface energy of the reaction system was minimal, the up-conversion nanocrystalline was formed rapidly. Using this method, we have prepared near-infrared photo-responsive nanopharmaceuticals as follows: (1) by continuous thermal injection, ultrasmall caf _ 2: Yb ~ (+) er fluorescent nanoparticles (10 nm).) have been prepared. By means of transmission electron microscope (TEM), X ray diffractometer, fluorescence spectrometer and so on, it was found that the concentration of Na ~ in the synthesis process could improve the crystallinity, fluorescence intensity and morphology of CaF2: YbPe er. It is also found that continuous thermal injection can effectively improve the fluorescence intensity of up-converted nanoparticles and can effectively control the size of up-converted nanoparticles, which proves that continuous thermal injection is a simple and efficient method. (2) on the basis of continuous thermal injection method, the near-infrared Guang Min drug NaYF4: YbChe TmPO-na-YF4 (UCNPs) @ mSiO2pCdSs was synthesized by layer self-assembly. By transmission electron microscopy, the size of the prepared UCNPsmon-CdS and mesoporous SiO-2 were 50 nm and 10 nm.X- ray spectrometer and nitrogen adsorption and desorption, respectively. It was found that UCNPssmSiO2 / CDs has good crystallinity and huge specific surface area (760 m2g-1). UCNPs' up-conversion fluorescence (380451 nm and 470nm) was quenched by semiconductor CDs via fluorescence energy resonance transfer process. By using the active free radical probe terephthalic acid, it was found that UCNPs stimulated CDs to produce hydroxyl radical (OH) under near-infrared irradiation. The photodegradation of Rhodamine B shows that UCNPs@ mSiOs has a high efficiency in producing active free radicals in near infrared light. At the same time, under the irradiation of 980nm near infrared light, the Guang Min drug UCNPs@ mSiO-1 / CDs was cultured with Hela cancer cells for 24 h, and the photodynamic therapy was studied. The experimental results showed that the prepared Guang Min drug system UCNPsr mSiOs 2% CDs had a good photodynamic therapy effect.
【学位授予单位】：合肥工业大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TQ460.1;TB383.1

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