【作者】 孙婷；

【导师】 王静媛； 李亚鹏；

【作者基本信息】 吉林大学 ， 高分子化学与物理， 2012， 硕士

【摘要】 量子点在癌症靶向诊断，细胞传导和光学成像技术方面具有巨大潜力。但是，设计一种安全无毒且发光效率高的靶向肿瘤细胞的探针，却仍然是个挑战。在本工作中，我们首先设计合成了一种两亲性梳状共聚物PASP-Na-DDA，制备了一系列DDA接枝率不同的两亲性共聚物，研究了接枝率对其水溶液性质的影响。通过比较它们的粒子尺寸，形态，包覆效率等因素，我们确定了用于修饰QDs的两亲性梳状聚合物的最佳疏水含量。然后，我们又把PEG接入梳状分子，制备了两亲性蜈蚣形共聚物PASP-Na-DDA-PEG。利用共聚物中的疏水烷基链与纳米粒子表面的油溶性配体之间的“疏水疏水作用”，把QDs包覆起来，将油溶性QDs转化为水溶性，使其可以应用于肿瘤的诊断和靶向治疗领域。经聚合物修饰后的水溶性量子点保持了与原量子点相同发光特性，说明我们的包覆过程并没有破坏量子点的晶格结构。研究还发现，PEG接枝率会影响量子点纳米粒子的性质。分析比较了一系列PEG接枝率不同的两亲性蜈蚣形共聚物包QDs后纳米粒子的流体力学直径和荧光发射光谱，确定出用于包覆QDs的两亲性蜈蚣形聚合物的最佳PEG接枝率。并测试了此时量子点纳米粒子的形貌。为了更准确的定位肿瘤位置，我们用能够特异性识别肝癌细胞的生物分子anti-VEGF与水溶性纳米粒子相连接，获得了对肝癌细胞具有靶向作用的纳米探针，提高了检测的准确度和灵敏。PEG的存在还能有效减少纳米探针与细胞的非特异性连接，同时降低纳米探针的毒性。本论文的研究在癌症早期诊断和靶向治疗领域将有重要意义。更多还原

【Abstract】 Semiconductor QDs are a new class of fluorescent labeling agents and haverecently been used for a broad range of biological applications. This broad interest isdriven by their unique optical and electronic properties such as size tunable lightemission, superior signal brightness, resistance to photobleaching, and simultaneousexcitation of multiple fluorescence colors. Thus, these QDs show promise asfluorescent probes for cell labeling and tracking. However, hydrophobic QDsprepared in organic phase make them insoluble in physiological solution, which to alarge extent limits their application in bioengineering. In this paper, we synthesis anovel class of amphiphilic centipede-like copolymer PASP-Na-DDA-PEG, totransfer hydrophobic octadecylamine–coated CdSe/ZnS QDs into hydrophiphilicones via surface modification.As we all know, aspartic acid is a kind of natural amino acid. The amphiphiliccopolymer we prepare is derivated from aspartic acid. Polymer itself can degradeinto non-toxic molecules that do no harm to environment.The amphiphilic comb copolymer PASP-Na-DDA was synthesized by thermalcondensation of aspartic acid (ASP) and aminolysis by dodecylamine (DDA),followed by hydrolysis of the remaining succinimide units in the copolymerbackbone. We synthesized a series of amphiphilic comb copolymer with differentDDA grafting level. The ratio of hydrophiphilic and hydrophobic chain werecontrolled by the regants. Then we studied the effect of grafting level on micellarbehavior in water solution. CMC, hydrodynamic diameter and micellar morphologywere determined. Considering all the factors above, we supposed the optimum polymer used for QDs modification was the one with DDA grafting level of40%.Experiments demonstrated comb-shape copolymer could be used to prepare denseand small nanoparticles.As is well known, PEG is widely used in bioengineering system because it issoluble and biocompatible. So we consider to graft PEG into the comb copolymer, toprepare amphiphilic centipede-like copolymer PASP-Na-DDA-PEG. We found theproperties of QDs nanocomposites, including particle size, optical propertie andmorphology, were affected by PEG chain density of the polymer coating. ComparedHD and PL spectra of QDs nanocomposites, with different PEG grafting level from0~60%. Results indicated that when PEG grafting level was40%, QDsnanocomposites showed the smallest size (105nm), and simultaneously exhibitedsuperior fluorescent properties among all the nanocomposites. These shell/corespherical structural nanoparticles were well dispersed in water, and did not formlarge aggregates. Apparently, polymer with PEG chain density of40%was theoptimum surface coating for QDs. The optical properties of QDs before and afterencapsulation were identical. The QDs nanocomposites in aqueous solutionpresented the same peak shape of absorption as initial QDs in chloroform), whichindicated that this transfer process didn’t destroy the structure of QDs nanocrystal.Finally, we studied the high-quality QDs nanocomposites, with VEGF antibodybinding to, served as a probe for tumor cell targeting and tracking. Anti-VEGF canspecificly recognize VEGF receptor which can be overexpressed by liver cancercells. Then we used the luminescence preporty of QDs to determine the location oftumor. This could improve the precision and sensitivity of cancer detection. PEGchain in the polymer coating limited nonspecific binding of QDs-anti-VEGF andcells and permitted cell receptors to access the antibody on the particle surface withhigh efficiency. PEG could effectively reduce the toxicity of QDs-anti-VEGFnanoprobe, which was demonatrated by Cytotoxicity Test.更多还原