稀土上转换纳米颗粒制备及其在药物递送、成像及检测中的应用

发布时间：2018-03-14 00:42

本文选题：稀土上转换纳米颗粒　切入点：药物递送　出处：《浙江大学》2017年硕士论文　论文类型：学位论文

【摘要】：稀土上转换纳米颗粒是一种近红外光激发下吸收低能光子,发射高能光子的新型发光材料,具有许多独特的优点,如光学和化学稳定性好、抗光漂白能力强、毒性低;此外近红外光激发具有组织穿透能力强、对生物组织无损伤、无背景荧光干扰等特点,因而稀土上转换纳米颗粒在生物医学领域受到了广泛关注,在生物传感、生物成像、疾病诊断等方面具有广阔的应用前景。基于稀土上转换纳米颗粒的上述优点和应用潜能,在本论文中,我们合成了形貌均一、晶型良好的稀土上转换纳米颗粒,并采用多种表面修饰方法来提高纳米粒子的亲水性和生物相容性;同时,我们成功构建了基于稀土上转换纳米颗粒的药物递送体系;此外我们初步探究了基于稀土上转换纳米颗粒的分子传感。本论文主要分为以下五章:第一章结合相关文献和研究背景,对稀土上转换纳米材料及其研究现状进行了介绍和综述,包括稀土上转换纳米材料的发光机制和组成、制备与表面修饰方法以及它们在生物传感、生物成像、诊断治疗等领域的应用,为本论文纳米材料合成、药物载体设计及应用研究、传感研究等提供理论基础和科学依据。第二章分别采用高温热解稀土油酸盐和稀土氯化物高温溶剂热法合成了形貌规则、粒径均一的六方晶型NaYF_4:Yb,Er上转换纳米粒子,相对而言,后者的上转换发光效率更高。此外我们采用不同的修饰方法对合成的疏水性纳米粒子进行了表面改性和功能化,使粒子具有更好的水溶性和生物相容性,为进一步偶联生物分子实现功能化奠定了良好的基础。第三章构建了基于稀土上转换纳米颗粒的多功能纳米药物平台用于肿瘤成像、药物递送和治疗。我们利用超分子组装法一步合成装载脂溶性前体药物和包覆聚乙二醇链的稀土上转换纳米药物,制备方法简便快捷。以7-乙基-10-羟基喜树碱(SN38)衍生物作为模型药物分子进行研究,该纳米载体的载药效率高达12.3%,并且具有缓慢而持续的药物释放动力学,有利于通过实体瘤的高通透性和滞留(Enhanced permeability and retention,简称 EPR)效应靶向输送到肿瘤部位。和临床使用的SN38前药——伊立替康(CPT-11)相比,我们的纳米药物表现出优越的小动物抗肿瘤效果。此外上转换荧光成像结果表明稀土上转换纳米药物载体可以成功应用于体内外成像,具有良好的稳定性和生物相容性,在成像介导的药物递送领域展现出广阔的应用前景。第四章利用单链DNA修饰的上转换纳米颗粒与氧化石墨烯之间的荧光共振能量转移,初步研究设计了一种简单检测三聚氰胺分子的光学传感器。后续工作主要集中在此传感器的灵敏度、选择性、检测范围等检测性能方面的优化及其在实际复杂样品中的检测应用。第五章对本论文工作进行总结,并就后续工作的开展提出展望。
[Abstract]:Rare earth upconversion nanoparticles are a new luminescent material which absorbs low energy photons and emits high energy photons under near-infrared excitation. It has many unique advantages, such as good optical and chemical stability, strong photobleaching resistance and low toxicity. In addition, near-infrared excitation has the characteristics of strong tissue penetration, no damage to biological tissue, no background fluorescence interference and so on. Therefore, rare earth up-conversion nanoparticles have attracted extensive attention in the field of biomedicine, such as biosensor, biomedical imaging, and so on. Based on the advantages and potential of rare-earth up-conversion nanoparticles, we have synthesized rare-earth up-conversion nanoparticles with uniform morphology and good crystal shape in this paper. Various surface modification methods were used to improve the hydrophilicity and biocompatibility of nanoparticles. At the same time, we successfully constructed a drug delivery system based on rare-earth upconversion nanoparticles. In addition, we preliminarily explore the molecular sensing based on rare earth upconversion nanoparticles. This thesis is divided into five chapters: chapter one combines relevant literature and research background. In this paper, the upconversion nanomaterials of rare earth and their research status are introduced and reviewed, including the luminescence mechanism and composition, preparation and surface modification methods of rare earth up-conversion nanomaterials, and their applications in biosensor and imaging. The applications in the field of diagnosis and treatment are the synthesis of nanomaterials in this paper, the design and application of drug carriers. The sensing research provides theoretical and scientific basis. In the second chapter, the homogenous hexagonal hexagonal crystal NaYF4: YbEr up-conversion nanoparticles were synthesized by high temperature solvothermal method of rare earth oleate and rare earth chloride, respectively. In addition, different modification methods were used to modify and functionalize the hydrophobic nanoparticles, which made the particles have better water solubility and biocompatibility. It lays a good foundation for further coupling biomolecules functionalization. In Chapter 3, a multifunctional nano-drug platform based on rare earth upconversion nanoparticles is constructed for tumor imaging. Drug delivery and treatment. We used supramolecular assembly to synthesize liposoluble precursor drugs and rare earth up-conversion nanopharmaceuticals coated with polyethylene glycol chains. The preparation method is simple and rapid. Using 7-ethyl-10-hydroxycamptothecin (SN38) derivative as a model drug molecule, the drug loading efficiency of the nano-carrier is as high as 12.3, and the drug release kinetics is slow and sustained. In comparison with the clinical use of SN38 prodrug Ilitecan, it is beneficial to target transport to the tumor site through the high permeability of solid tumor and retention enhanced permeability and retention.Compared with the clinical use of SN38 prodrug, Iritekam (CPT-11), EPRs can be transferred to the tumor site. Our nanopharmaceuticals show excellent anti-tumor effect in small animals. In addition, up-conversion fluorescence imaging results show that rare-earth up-conversion nano-drug carriers can be successfully used in vivo and in vitro imaging, with good stability and biocompatibility. In chapter 4th, fluorescence resonance energy transfer between graphene oxide and up-conversion nanoparticles modified by single strand DNA is presented. A simple optical sensor for the detection of melamine molecules was preliminarily studied and designed. The follow-up work mainly focused on the sensitivity and selectivity of the sensor. The optimization of detection performance and its application in practical complex samples. Chapter 5th summarizes the work of this paper and puts forward the prospects for the future work.
【学位授予单位】：浙江大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：TB383.1;TQ460.1

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