【作者】 陶惠泉；

【导师】 刘庄；

【作者基本信息】 苏州大学 ， 细胞生物学， 2012， 硕士

【摘要】 由于碳元素是生命的基本组成元素，具有无毒，环保，稳定性好等众多优点，所以主要由碳元素构成的碳基纳米材料在生物医学应用中具有天然的优势。碳纳米点与石墨烯是近些年来新发现的两种碳基纳米材料。由于具有独特的材料学特性，它们在生物医学应用中得到广泛的关注。在这篇论文中，我们研究了荧光碳点与磁性纳米石墨烯在生物成像以及药物输送中的应用。以混酸氧化破碎单壁碳管是一种常见的标准操作，其过程会产生一种能发出荧光的棕黄色液体。以往认为这种液体的主要成分是超短碳管。可是经我们研究发现，这种液体实际上是由一种直径在3到5纳米的碳点构成的。我们尝试用同样的条件处理了多壁碳管以及石墨，结果也获得了同样的碳点。这种荧光碳点的表面具有丰富的含氧基团，所以具有极佳的水溶性。与其他碳点类似，这种碳点也具有激发光波长依赖性的荧光。我们为了进一步利用它的这种性质，尝试把这种碳点溶液注射入裸鼠的皮下，而后使用小动物成像系统进行成像。结果发现这种碳点可以在皮下被各种波长的激发光激发出荧光，而其中以近红外光激发荧光成像的信噪比最高，成像效果最佳。为配合这种荧光碳点在生物医学研究中的进一步应用，我们又系统的研究了这种碳点的体内体外毒性，血液循环时间以及生物分布与排泄。结果显示这种碳点几乎没有毒副作用，而且由于具有极小的尺寸，除经传统的粪便途径排泄，还可以经尿液排出，具有极佳的生物医学应用前景。在另外一项平行的工作中，我们还选用经化学共沉淀法制备的磁性纳米石墨烯复合物进行了药物输送与生物成像研究。之前已有研究者进行过相关的研究，但是他们仅仅局限于体外实验，未曾进行过体内实验。为了将这种材料用于体内实验，我们首先要通过对其进行表面修饰以提高它的生物稳定性。聚乙二醇常被用来修饰纳米石墨烯，以提高纳米石墨烯的生物稳定性。我们也决定用这个方法来修饰磁性纳米石墨烯。修饰后得到的聚乙二醇磁性纳米石墨烯表现出优异的生物稳定性。我们进一步尝试给聚乙二醇磁性石墨烯装载上抗癌药物阿霉素，而后在外磁场引导下将这一复合物富集到细胞培养皿的特定的部位并特异性杀伤了这一部位的细胞，成功实现了体外的磁靶向性药物输送与治疗。考虑到纳米石墨烯优异的光热吸收能力，我们又尝试使用聚乙二醇磁性纳米石墨烯进行了磁靶向性光热治疗，并也获得了成功。最后，我们直接将聚乙二醇磁性纳米石墨烯注射入小鼠体内进行核磁T2成像，结果使T2成像明显增强。虽然，我们还未全面系统地研究这一材料的药代动力学，生物毒性等方面的性质，但毕竟开启了以纳米石墨烯为基质的磁性纳米材料的活体成像之门。总之，我们的工作揭示了荧光碳纳米点和磁性纳米石墨烯复合材料在生物成像与药物输送中的令人鼓舞应用前景，为进一步进行探索这一类低维碳纳米材料的医学应用奠定了基础。更多还原

【Abstract】 Carbon-based nanomaterials were considered to have great potential in thebiomedicine with the features of environment-friendly composition, low toxicity, andgood stability. Carbon dots and graphene are carbon-based nanomaterials discovered inrecent years With great potential in biomedicine.In this thesis, we investigate the biomedical applications of carbon dots andmagnetic nano-graphene for bioimaging and drug delivery.Oxidization of carbon nanotubes by a mixed acid has been utilized as a standardmethod to functionalize carbon nanomaterials for years.Here,the products obtained fromcarbon nanotubes and graphite after a mixed-acid treatment are carefully studied.Nearlyidentical carbon dot(Cdot)products with diameters of3–4nm are produced using thisapproach from a variety of carbon starting materials,including single-walled carbonnanotubes,multiwalled carbon nanotubes,and graphite.These Cdots exhibit strongyellow fluorescence under UV irradiation and shifted emission peaks as the excitationwavelength is changed.In vivo fluorescence imaging with Cdots is then demonstrated inmouse experiments,by using varied excitation wavelengths including some in thenear-infrared(NIR)region.Furthermore,in vivo biodistribution and toxicology of thoseCdots in mice over different periods of time are studied;no noticeable signs of toxicityfor Cdots to the treated animals are discovered.This work provides a facile method tosynthesize Cdots as safe non-heavy-metal-containing fluorescent nanoprobes,promisingfor applications in biomedical imaging.Two-dimensional graphene and its composite nanomaterials offer interestingphysical/chemical properties and have been extensively explored in a wide range offields in recent years.In this work,we synthesize a multi-functional superparamagneticgraphene oxide–iron oxide hybrid nanocomposite(GO–IONP),which is thenfunctionalized by a biocompatible polyethylene glycol(PEG)polymer to acquire high stability in physiological solutions.A chemotherapy drug,doxorubicin(DOX),was loadedonto GO–IONP–PEG,forming a GO–IONP–PEG–DOX complex,which enablesmagnetically targeted drug delivery.GO–IONP–PEG also exhibits strong opticalabsorbance from the visible to the near-infrared(NIR)region,and can be utilized forlocalized photothermal ablation of cancer cells guided by the magneticfield.Moreover,for the first time,in vivo magnetic resonance(MR) imaging oftumor-bearing mice is also demonstrated using GO–IONP–PEG as the T2contrastagent.Our work suggests the promise of using multifunctional GO-basednanocomposites for applications in cancer theranostics.In summary, our results show the promising of using fluorescent Cdots andmagnetic nano-graphene composites for bioimaging and drug delivery, and encouragefurther exploration of those low-dimensional carbon nanomaterials in biomedicine.更多还原