基于pH响应的荧光纳米硅球的制备及应用

发布时间：2018-06-23 13:06

本文选题：荧光纳米硅球 + 反相微乳液法　；参考：《河北大学》2017年硕士论文

【摘要】：近几年来,环境污染愈来愈严重,食品安全问题愈演愈烈,人类的健康受到严重威胁,新增癌症病例逐年递增,研发有效的检测手段和抗癌方法已刻不容缓。随着纳米技术的发展,荧光纳米材料在整个生物医学领域的地位日益凸显。为了满足医疗技术的需要,荧光纳米材料逐渐向着生物相容性好、荧光信号稳定高效、特异性强、易功能化等方向发展。鉴于酸碱度对生物体生命活动的重要调控作用,以及生命现象的发生和细胞内pH值的变化密切相关,在众多功能化荧光纳米材料中,具有pH响应性的荧光纳米硅球以其优良的性能脱颖而出。由于pH响应性能不仅可以来自荧光染料本身,还可以通过pH响应性功能基团修饰获得,因此,本文制备了两种不同的荧光纳米硅球,并对其在pH传感器和药物释放等方面的应用进行了初步研究。本论文以异硫氰酸类荧光染料为荧光源,选用生物相容性良好且表面易修饰的硅胶为载体制备荧光纳米硅球。首先综述了荧光纳米颗粒及pH响应性材料的分类、合成方法及潜在的应用前景,阐述了本文研究意义。利用硅烷偶联剂γ-氨丙基三乙氧基硅烷(APTES)在其氨基与异硫氰根加成生成Schiff碱的同时,还能与TEOS发生水解缩合的特点,制备键合异硫氰酸荧光素(FITC)的荧光纳米硅球。根据FITC在微球中位置的不同,荧光硅球将有两种结构——包覆型(c-FSNs)与表面接枝型(s-FSNs)。对其性能进行比较分析发现:与表面接枝型型相比,包覆型荧光硅球光漂白程度低,光稳定性良好,其中,利用反相微乳液法(W/O)包硅制备的包覆型荧光纳米硅球比St?ber法粒径更小易控,荧光信号较强,且具有介孔结构,更利于生物医药等方面的应用。将c-FSNs作为pH传感器研究,发现其响应迅速,荧光强度在pH 5.2-7.8内几乎呈线性增长,pKa约6.32,且具有良好的可逆性、重现性、准确性和生物相容性。基于聚丙烯酸(PAA)具有pH响应性的特点,本文以RITC-APTES作荧光前驱体,采用W/O法合成键合异硫氰酸罗丹明B(RITC)的介孔荧光纳米硅球(FMSNs),表面氨基化修饰后,经过酰胺反应,连接PAA,制备具有pH响应性的荧光纳米硅球(PAA-FMSNs),经表征,制得的微球粒径均一,约181 nm,分散性良好,孔径16.6 nm,比表面积17.3 m2?g-1,生物相容性良好;接着,以盐酸阿霉素(DOX)为模型药物,研究PAA-FMSNs作为p H响应性纳米药物载体的能力,数据表明DOX∶PAA-FMSNs为1.5时,荧光纳米硅球载体具有较高的包封率(94.5%)和载药量(58.6%),且在pH 5.4-7.4的范围内,随pH的降低,药物释放率明显升高,具有显著的pH响应性。
[Abstract]:In recent years, environmental pollution has become more and more serious, food safety has become more and more serious, human health has been seriously threatened, new cases of cancer have been increasing year by year, it is urgent to develop effective detection methods and anticancer methods. With the development of nanotechnology, fluorescent nanomaterials play an increasingly important role in the field of biomedicine. In order to meet the needs of medical technology, fluorescent nanomaterials are developing towards good biocompatibility, stable and efficient fluorescent signals, strong specificity and easy functionalization. In view of the important regulation of pH on biological activity and the close relationship between the occurrence of life phenomena and the change of intracellular pH value, among the many functionalized fluorescent nanomaterials, Ph-responsive fluorescent nanocrystalline silica spheres stand out for their excellent properties. Since the pH response properties can be obtained not only from the fluorescent dyes themselves, but also through the modification of pH responsive functional groups, two kinds of fluorescent nanocrystals were prepared in this paper. Its application in pH sensor and drug release was studied. In this paper, fluorescent nanocrystalline silica spheres were prepared by using isothiocyanate dyes as fluorescent source and silica gel with good biocompatibility and easy surface modification. The classification, synthesis methods and potential application prospects of fluorescent nanoparticles and pH responsive materials are reviewed. Using silane coupling agent 纬 -aminopropyltriethoxysilane (APTES) to form Schiff base by addition of amino and iso-thiocyanate, the fluorescent nanospheres bonded with fluorescein isothiocyanate (FITC) were prepared by hydrolysis and condensation with TEOS. According to the position of FITC in microspheres, there will be two structure-cladding type (c-FSNs) and surface grafting type (s-FSNs). Compared with the surface grafting type, the coated fluorescent silicon sphere has low photobleaching degree and good photostability. The coated fluorescent nanocrystalline silica spheres prepared by the reverse microemulsion method (W / O) are smaller and easier to control than the Stouber method. The fluorescence signal is stronger and has mesoporous structure, which is more suitable for biomedical applications. Using c-FSNs as pH sensor, it was found that the response of c-FSNs was rapid, and the fluorescence intensity increased linearly about 6.32 in pH 5.2-7.8, and had good reversibility, reproducibility, accuracy and biocompatibility. Based on the pH response of polyacrylic acid (PAA), a mesoporous fluorescent nanospheres (FMSNs) bonded with Rhodamine isothiocyanate B (RITC) were synthesized by W / O method using RITC-APTES as fluorescence precursor. The fluorescent nanospheres (PAA-FMSNs) with pH response were prepared by linking PAA. The microspheres were characterized by uniform particle size, about 181 nm, good dispersibility, good pore size 16.6 nm, specific surface area 17.3 m2 路g -1, good biocompatibility, and doxorubicin hydrochloride (DOX) as the model drug. The ability of PAA-FMSNs as pH responsive nano-drug carrier was studied. The results showed that when DOX: PAA-FMSNs was 1.5, the encapsulation efficiency (94.5%) and drug loading (58.6%) of fluorescent silica nanoparticles were higher, and the pH value decreased with pH 5.4-7.4, and the results showed that PAA-FMSNs had high encapsulation efficiency (94.5%) and drug loading (58.6%) when DOX: PAA-FMSNs was 1.5. The drug release rate was significantly increased, and had significant pH response.
【学位授予单位】：河北大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O613.72;TB383.1

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