CN107007845B - 一种碳酸锰纳米复合材料在磁共振成像中的应用 - Google Patents

一种碳酸锰纳米复合材料在磁共振成像中的应用 Download PDF

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CN107007845B
CN107007845B CN201710265995.8A CN201710265995A CN107007845B CN 107007845 B CN107007845 B CN 107007845B CN 201710265995 A CN201710265995 A CN 201710265995A CN 107007845 B CN107007845 B CN 107007845B
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manganese carbonate
polydopamine
magnetic resonance
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陈志伟
黄建攀
周樨
任磊
程友星
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Abstract

本发明提供了一种碳酸锰纳米复合材料在磁共振成像(MRI)中的应用。所述的碳酸锰核的粒径为80‑120nm，包覆层聚多巴胺的厚度在10‑30nm。此外，这种高分子聚合物具有生物相容性好等优点。因而，这种具有增强磁共振造影性能的锰基纳米造影剂在医学影像诊断领域具有广阔的应用价值。

Description

一种碳酸锰纳米复合材料在磁共振成像中的应用
技术领域
本发现涉及一种碳酸锰纳米复合材料在磁共振成像中的应用。
背景技术
核磁共振成像(Magnetic Resonance Imaging，MRI)由于其具有高成像分辨率、无电离辐射、同时能提供多层次诊断信息的特点，已经广泛运用于医学成像检测中。目前临床上广泛使用的T1造影剂为Gd(Ⅲ)的螯合物，因为三价钆离子的最外层有七个未成对电子，有很强的顺磁性。然而，最近研究指出以Gd3+为基的造影剂会导致肾源性系统性纤维化，这使得以镧系金属为基材料特别是钆基复合材料造影剂在临床上的运用受到很大限制(Shin,T.H.；Choi,Y.；Kim,S.；Cheon,J.,Recent advances in magnetic nanoparticle-based
multi-modal imaging.Chem Soc Rev 2015,44(14),4501-4516.)。因此，人们将更多的注意力转移到最外层有五个未成对电子且同样具有T1造影作用的金属离子Mn2+上，旨在研发更加安全有效的T1造影剂。近年来，人们对氧化锰无机纳米粒子是研究越来越多，然而制备出来的颗粒显影效果并不明显，即r1值较低。
发明内容
本发明的主要目的在于提供一种聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料在磁共振成像MRI中的用途，其中：所述的碳酸锰核的粒径为80-120nm，包覆层聚多巴胺的厚度在10-30nm。
本发明的另一目的在于提供聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料作为磁共振成像MRI中的材料用途，所述的碳酸锰核的粒径为80-120nm，包覆层聚多巴胺的厚度在10-30nm。
其中，所述的聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料在MRI诊断中作为T1造影剂。
在本发明中，所述的聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料可以采用如下方式获得：1)微乳合成法，使用环己烷作为有机相溶剂，十六烷基三甲基溴化铵(CTAB)作为表面活性剂，正戊醇作为助溶剂，以及氯化锰和碳酸铵水溶液作为水相形成油包水的纳米体系，在室温下搅拌便可合成碳酸锰纳米颗粒。再将得到的碳酸锰经聚丙烯酸钠修饰后再进行聚多巴胺包覆，便可形成聚多巴胺包覆碳酸锰复合纳米材料。本发明中，所述的聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料，也可以采用其它方式获得。本发明的重点在于这种材料的新用途。
本发明涉及基于聚多巴胺增强碳酸锰造影性能的纳米材料在磁共振成像中的应用具有以下优点：
1)该粒子粒径均匀，呈平行六面体形，具有较大的比表面积，且根据需要可以调控包覆层聚多巴胺的厚度，10-30nm。
2)聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米粒子具有良好的水分散性和稳定性，冷冻干燥后可长时间保存。
3)具有良好的T1造影效果，r1值为6.2mM-1s-1。
4)申请人发现聚多巴胺包覆在碳酸锰纳米粒子表面之后能够明显的提高其r1值。因此，申请人提出了在包覆聚多巴胺前后纳米粒子在MRI成像方面的应用。
5)申请人发现碳酸锰本身具有较好的造影性能，但是再经聚多巴胺包覆之后其造影性能进一步提升，可以作为一种良好的磁共振成像检测试剂
6)用于磁共振成象检测。
附图说明
图1是实施例1中的MnCO3纳米粒子的扫描电镜照片(Scanning ElectronMicroscope，SEM)。
图2是实施例1中的MnCO3@PDA纳米粒子的X射线衍射谱(X-ray powderdiffraction，XRD)。
图3是实施例1中的MnCO3@PDA纳米粒子的透射电镜照片(Transmission ElectronMicroscope,TEM)。
图4是实施例1中的MnCO3和MnCO3@PDA纳米粒子的T1加权像照片和T1弛豫时间倒数与Mn浓度的线性关系图。
具体实施方式
下面结合实施例和附图对本发明做进一步的说明。
材料制备：
1、碳酸锰纳米颗粒：量取50mL环己烷，4mL正戊醇和0.6mL 0.5M/L氯化锰溶液于100mL烧杯中混合均匀，然后称取4g CTAB于上述混合溶液中，整个混合体系置于超声波清洗器不断超声直至固体粉末完全溶解，溶液变得澄清透明为止。随后再向其中逐滴加入0.6mL 0.5M/L碳酸铵溶液，室温下不断搅拌2h。待反应结束后所得产物离心分离(10000rpm，10min)，并先用无水乙醇洗涤2次，超纯水洗涤3次。
2、聚丙烯酸(PAA)修饰碳酸锰纳米粒子：首先称取100mg PAA(分子量约为3000)于100mL水中，待其完全分散后，使用浓度为0.5M/L Na2CO3溶液调节其pH至8.0左右得到PAA钠盐待用。将20mg所合成的碳酸锰纳米粒子分散于80mL超纯水中超声10min，等到粒子在水中均匀分散后置于磁力搅拌器上搅拌10min，再向其中加入2.5mL浓度为1mg/mL的PAA钠盐继续室温搅拌24h。所得产物离心分离(12000rpm,10min)，纯水洗涤3次后分散于水中，确定其浓度为5mg/mL。样品保存于4℃冰箱中。
3、聚多巴胺包覆碳酸锰的合成：首先配制10mM的三羟基氨基甲烷盐酸(Tris-HCl)缓冲液：称取0.242g Tris置于200mL水中搅拌直至完全溶解，然后使用0.5M盐酸和碳酸钠溶液调节其pH至8.5待用。将2.5mg聚丙烯酸修饰的碳酸锰纳米粒子分散于30mL 10mMTris-HCl溶液超声分散，然后向其中加入1.0-4.0mg盐酸多巴胺。整个体系放在超声破碎仪上超声30min，最后接着超声振荡4h。采用离心分离(12000rpm,10min)的方式除去未反应的多巴胺材料，所得的MnCO3@PDA纳米颗粒使用超纯水洗涤3次后分散于水中。
实施例1：
一种基于聚多巴胺增强碳酸锰造影性能的纳米材料在磁共振成像中的应用，步骤如下：
1)首先取一定量的样品按照1:9的比例消解于新配置的王水中，后用新配3％的HNO3按照1:9的比例稀释至一定浓度。
2)使用电感耦合等离子共振仪(ICP-MS)精确标定碳酸锰和聚多巴胺包覆碳酸锰粒子中锰离子的含量，最终测得Mn2+浓度分别为20.1095mM和4.4855mM，后按照稀释比例逆推算出样品浓度。
3)首先分别取上述已标定浓度的碳酸锰纳米悬液0，1μL，2.5μL，4μL，5μL，10μL于1.5mL的离心管内，再分别向相应管内加入500μL，499μL，497.5μL，496μL，495μL和490μL的超纯水，确保每管中含有溶液体积为500μL；
再取上述已标定浓度的聚多巴胺包覆碳酸锰纳米悬液0，4.5μL，11.1μL，17.8μL，22.3μL，44.6μL于1.5mL的离心管内，再分别向相应的管内加入500μL，495.4μL，488.9μL，482.2μL，477.7μL，455.4μL的超纯水，确保每管中含有溶液体积为500μL。
4)然后向以上每管中再加入500μL浓度为2％的热琼脂溶液，并且用旋磁震荡仪1000rpm，2min，确保混合混匀，常温放置直至溶液固定。
5)将配好的溶液置于7T小动物成像仪(Agilent Technologies,Santa Clara,CA,USA)内进行MRI信号采集，测试参数设定：TR＝3000ms，TE＝15ms，视野为45×45mm。
结果见图1至图4
图1为实施例1中的MnCO3纳米粒子的SEM照片，从图1中可以看出，所制备的碳酸锰纳米粒子边长约为100nm，平均对角线长约为140nm。
图2是实施例1中的MnCO3@PDA纳米粒子的X射线衍射谱，从图谱中可以看到碳酸锰样品的衍射峰，没有检测到第二相，说明经过聚多巴胺包覆后碳酸锰没有发生物相变化。
图3是实施例1中的MnCO3@PDA纳米粒子的TEM图片，可以看到所制备的聚多巴胺包覆碳酸锰纳米粒子对角线长平均在170nm。
图4是实施例1中的MnCO3和MnCO3@PDA纳米粒子的T1成像照片和T1弛豫时间倒数与Mn浓度的线性关系图，可以看到所制备的碳酸锰纳米粒子的弛豫率为5.3mM-1s-1，但是经过聚多巴胺包覆后得到的MnCO3@PDA纳米粒子的弛豫率进一步提高，达到了6.3mM-1s-1，因而在MRI诊断中可作为良好的T1造影剂。

Claims (2)

1.聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料在制备磁共振成像MRI材料中的用途，其特征在于：所述的碳酸锰核的粒径为80-120nm，包覆层聚多巴胺的厚度在10-30nm。
2.如权利要求1所述的聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料在制备磁共振成像MRI材料中的用途，其特征在于：所述的聚多巴胺包覆碳酸锰(MnCO3@PDA)复合纳米材料在MRI诊断材料中作为T1造影剂。
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