CN108714223A - 一种兼具磁共振和荧光双重成像特性的造影剂及其制备方法 - Google Patents
一种兼具磁共振和荧光双重成像特性的造影剂及其制备方法 Download PDFInfo
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Abstract
一种兼具磁共振和荧光双重成像特性的造影剂及其制备方法，属于兼具磁共振和荧光双重成像特性纳米粒子的制备技术领域。它是以无机纳米粒子为结构基础，通过在其骨架中掺杂具有磁共振成像的离子，然后采用后嫁接、离子交换等方法将聚集诱导发光分子修饰到无机纳米粒子中，从而制得兼具磁共振和荧光双重成像特性的造影剂纳米材料。该方法适用于多种磁性离子的氯化盐及聚集诱导发光分子，得到可在水溶液中均匀分散的，粒径约为50nm的纳米材料。该类材料具有良好的生物相容性、较强的蓝色荧光和磁共振成像性能，在生物医学成像等领域展现潜在的应用价值。
Description
技术领域
本发明属于兼具磁共振和荧光双重成像特性纳米粒子的制备技术领域，具体涉及一种兼具磁共振和荧光双重成像特性的造影剂及其制备方法，该造影剂在医学诊断等方面具有潜在的应用价值。
背景技术
荧光生物探针是一种有效的光学成像方式，可以高效的标记出生物组织的复杂结构，具有高效、成本低等优势。到目前为止，许多荧光功能性纳米材料被开发出来，并作为一种新颖的发光材料广泛应用于生物医学、化学检测、固体发光等领域。聚集诱导发光材料是一种特殊的荧光生色团，在良溶剂状态时几乎没有荧光，而在固态或者聚集态时具有较高的荧光量子效率。自该类分子被首次报道以来，越来越多具有该类特性的有机分子被合成出来，其发光范围从蓝光到红光几乎覆盖整个可见波长，并广泛应用于检测、细胞成像、有机光电二极管等领域。分子内移动受限是该类材料具有较强荧光特性的主要原因。然而，单一荧光成像的组织穿透能力较弱，仅能应用到人体表面或近表面成像，很难满足高灵敏度、高空间分辨率的效果。
核磁共振成像主要利用外加磁场，根据不同组织中质子的纵向弛豫时间及横向弛豫时间来判断其成像效果，具有较高的空间分辨率和较深的穿透能力，是实际应用比较广泛的诊断方法之一。由于核磁共振成像的清晰度不高、灵敏度较低，限制了该类材料的进一步发展。因此，将核磁共振成像与荧光成像的功能复合到单一结构的纳米材料中，能够有效克服各自成像方法的局限性，获得更加清晰的内部组织信息。朱君等人(CN 103845741 A)以介孔二氧化硅为介质，通过同时连接荧光分子和钆鳌合物得到具有荧光磁共振双模式造影剂，但该方法制备相对复杂，且荧光分子易发生荧光淬灭的现象，且材料不能在水溶液中长期稳定存在；窦红静等人(CN 106902360 A)将纳米凝胶分别与核磁显影分子及荧光分子偶联制备磁共振、荧光双显影功能化的纳米材料，但荧光分子甲基菁染料易发生光漂白现象。因此制备一种合成方法简单、生物相容性好、水分散性优异、荧光稳定并兼具磁共振和荧光双重成像特性的纳米材料显得尤为重要。
本发明制备的纳米复合材料具有制备方法简单、成分可调、生物相容性好、水分散性优异等特点，在水溶液中具有较强的蓝色荧光和磁共振成像性能，在医学诊断等方面展现潜在的应用价值。
发明内容
本发明的目的在于一种兼具磁共振和荧光双重成像特性的造影剂及其制备方法，是以无机纳米粒子为结构基础，通过在其骨架中掺杂具有磁共振成像的离子，然后采用后嫁接、离子交换等方法将聚集诱导发光分子修饰到无机纳米粒子中，从而制得兼具磁共振和荧光双重成像特性的造影剂纳米材料。
该方法适用于多种磁性离子的氯化盐及聚集诱导发光分子，得到可在水溶液中均匀分散的，粒径约为50nm的纳米材料。该类材料具有良好的生物相容性、较强的蓝色荧光和磁共振成像性能，在生物医学成像等领域展现潜在的应用价值。
本发明所述的一种兼具磁共振和荧光双重成像特性的造影剂的制备方法，其步骤如下：
(1)将0.5～2.3g金属氯化盐超声溶解于20mL无水乙醇和0～20mL水组成的混合溶液中，将0.5～1.5g磷源或硅源加入到上述溶液中，用1mol/L的氢氧化钠水溶液调节溶液的pH值至9～13，室温条件下继续搅拌10～24h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
(2)将0.2g步骤(1)制备的纳米材料超声分散于5～10mL二甲基亚砜溶液中，将0.005～0.015g聚集诱导发光分子加入到上述溶液中，70～90℃条件下避光搅拌20～30h，冷却至室温后，将溶液倒入无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂纳米材料。
所述的金属氯化盐为氯化钆、氯化铁、氯化锰中的一种或两种；磷源为磷酸或阿仑膦酸钠；硅源为正硅酸乙酯或氨丙基三乙氧基硅烷；含有反应基团的有机荧光聚集诱导发光分子，其结构式如下之一所示：
本发明首次制备了一种兼具磁共振和荧光双重成像特性的造影剂，其具有如下优点：
1.本发明制备的兼具磁共振和荧光双重成像特性的造影剂，具有操作方法简单，制备成本低等优势，且材料同时具有良好的生物相容性，在医学成像等领域具有良好的应用前景。
2.本发明制备的造影剂粒径小，在水溶液中具有良好的分散性，适合应用于细胞成像。
3.通过调节聚集诱导发光分子的种类，可以制备不同荧光颜色的纳米粒子，有利于进一步提高细胞成像的灵敏性和准确性。
附图说明
图1：为本发明实施例1中造影剂的荧光谱图；
图2：为本发明实施例1造影剂的日光(a)及荧光照片(b)；
图3：为本发明实施例1中造影剂的扫描电镜图；
图4：为本发明实施例1中造影剂的透射电镜图；
图5：为本发明实施例1中造影剂的细胞成像图；
图6：为本发明实施例1中造影剂的核磁共振图；
图7：为本发明实施例1中造影剂的细胞相容性图；
如图1、2所示：在360nm紫外光激发下，造影剂在480nm处有较强的荧光发射峰，表现出强的蓝色荧光。造影剂的日光照片(a)表明该材料能够均匀分散到水溶液中，且具有良好的透过率，荧光照片(b)进一步证明造影剂具有强的荧光。
如图3所示：造影剂呈现球形聚集态，粒径约50nm。
如图4所示：透射电镜造影剂在水溶液中均匀分散成粒径较小的纳米粒子。
如图5所示：细胞的日光照片(a)和荧光照片(b)，从照片中发现有荧光的地方均存在有细胞，表明造影剂己经成功进入到细胞中，并能够用于细胞成像。
如图6所示：随着造影剂中钆离子浓度的增加，核磁成像的亮度也在逐渐增加，展现良好的核磁共振成像效果。
如图7所示：在造影剂浓度为0.2mg/mL的条件下，细胞仍有较高的成活率，展现良好的生物相容性。
具体实施方式
下面通过实施例对本发明做进一步的描述，但本发明的实施方式不限于此，不能理解为对本发明保护范围的限制。
实施例1：
将2.3g氯化钆超声溶解于20mL无水乙醇溶液中，将1.5g硅源氨丙基三乙氧基硅烷加入到上述溶液中，用1mol/L氢氧化钠溶液调节pH值为13，室温条件下继续搅拌24h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
将0.2g步骤(1)制备的纳米材料超声分散于5mL二甲基亚砜溶液中，将0.005g的BTPE加入到上述溶液中，80℃条件下避光搅拌20h，冷却至室温后，将溶液倒入50mL无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂，产物质量是0.13g.
实施例2：
将0.5g氯化钆和1.8g氯化铁超声溶解于20mL无水乙醇和20mL水组成的混合溶液中，将1.0g磷源阿仑膦酸钠加入到上述溶液中，用1mol/L的氢氧化钠溶液调节pH值为9，室温条件下继续搅拌10h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
将0.2g步骤(1)制备的纳米材料超声分散于10mL二甲基亚砜溶液中，将0.005g的TPE-CHO加入到上述溶液中，80℃条件下避光搅拌24h，冷却至室温后，将溶液倒入50mL无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂，产物质量是0.14g。
实施例3：
将0.5g氯化铁超声溶解于20mL无水乙醇与10mL水构成的混合溶液中，将1.2g磷酸加入到上述溶液中，用1mol/L的氢氧化钠溶液调节pH值为9，室温条件下继续搅拌10h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
将0.2g步骤(1)制备的纳米材料超声分散于10mL二甲基亚砜溶液中，将0.015g的TPE-N加入到上述溶液中，80℃条件下避光搅拌30h，冷却至室温后，将溶液倒入50mL无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂，产物质量是0.13g。
实施例4：
将1.8g氯化锰超声溶解于20mL无水乙醇与20mL水构成的混合溶液中，将0.5g正硅酸乙酯加入到上述溶液中，用1mol/L的氢氧化钠水溶液调节pH值为12，室温条件下继续搅拌20h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
将0.2g步骤(1)制备的纳米材料超声分散于5mL二甲基亚砜溶液中，将0.01g的TPE-SO3Na加入到上述溶液中，80℃条件下避光搅拌30h，冷却至室温后，将溶液倒入50mL无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂，产物质量是0.15g。
Claims (5)
1.一种兼具磁共振和荧光双重成像特性的造影剂制备方法，其步骤如下：
(1)将0.5～2.3g金属氯化盐超声溶解于20mL无水乙醇和0～20mL水组成的混合溶液中，将0.5～1.5g磷源或硅源加入到上述溶液中，用1mol/L的氢氧化钠水溶液调节溶液的pH值至9～13，室温条件下继续搅拌10～24h，离心分离，干燥后制得具有磁共振成像特性的纳米材料；
(2)将0.2g步骤(1)制备的纳米材料超声分散于5～10mL二甲基亚砜溶液中，将0.005～0.015g聚集诱导发光分子加入到上述溶液中，70～90℃条件下避光搅拌20～30h，冷却至室温后，将溶液倒入无水乙醇中，离心分离，干燥后得到兼具磁共振和荧光双重成像特性的造影剂纳米材料。
2.如权利要求1所述的一种兼具磁共振和荧光双重成像特性的造影剂制备方法，其特征在于：金属氯化盐为氯化钆、氯化铁、氯化锰中的一种或两种。
3.如权利要求1所述的一种兼具磁共振和荧光双重成像特性的造影剂制备方法，其特征在于：磷源为磷酸或阿仑膦酸钠；硅源为正硅酸乙酯或氨丙基三乙氧基硅烷。
4.如权利要求1所述的一种兼具磁共振和荧光双重成像特性的造影剂制备方法，其特征在于：聚集诱导发光分子的结构式如下之一所示，
5.一种兼具磁共振和荧光双重成像特性的造影剂，其特征在于：是由权利要求1～4任何一项所述的方法制备得到。
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110231316A (zh) * | 2019-04-26 | 2019-09-13 | 山西医科大学 | 双模态纳米探针的制备及其对间充质干细胞的标记及成像 |
| CN112741907A (zh) * | 2020-11-06 | 2021-05-04 | 浙江大学 | 用于干细胞示踪的磁共振-荧光双模态对比剂及其制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101741998B1 (ko) * | 2015-12-15 | 2017-05-31 | 세종대학교 산학협력단 | 바이러스 벡터의 유전자 전달 증진을 위한 아미노프로필마그네슘필로실리케이트 또는 아미노프로필칼슘필로실리케이트의 용도 |
| CN106939163A (zh) * | 2017-03-13 | 2017-07-11 | 吉林大学 | 一种高度水分散性的荧光功能化有机粘土的制备方法 |
-
2018
- 2018-05-31 CN CN201810548416.5A patent/CN108714223B/zh active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101741998B1 (ko) * | 2015-12-15 | 2017-05-31 | 세종대학교 산학협력단 | 바이러스 벡터의 유전자 전달 증진을 위한 아미노프로필마그네슘필로실리케이트 또는 아미노프로필칼슘필로실리케이트의 용도 |
| CN106939163A (zh) * | 2017-03-13 | 2017-07-11 | 吉林大学 | 一种高度水分散性的荧光功能化有机粘土的制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| YOUNG-CHUL LEE等: ""Optical Properties of Fluorescein-labeled Organoclay"", 《PHOTOCHEMISTRY AND PHOTOBIOLOGY》 * |
| 孙家干等: ""聚氨酯 /无机粒子纳米复合材料的"", 《合成橡胶工业》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110231316A (zh) * | 2019-04-26 | 2019-09-13 | 山西医科大学 | 双模态纳米探针的制备及其对间充质干细胞的标记及成像 |
| CN110231316B (zh) * | 2019-04-26 | 2022-01-21 | 山西医科大学 | 双模态纳米探针的制备及其对间充质干细胞的标记及成像 |
| CN112741907A (zh) * | 2020-11-06 | 2021-05-04 | 浙江大学 | 用于干细胞示踪的磁共振-荧光双模态对比剂及其制备方法 |
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