CN109550058A - 具有连续发光和弛豫性能的锰基纳米粒及其制备方法 - Google Patents
具有连续发光和弛豫性能的锰基纳米粒及其制备方法 Download PDFInfo
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Abstract
一种具有弛豫性能和可连续发光锰基纳米粒及其制备方法,该制备方法包括:A)以油酸锰为前驱体,热分解制备锰基纳米粒;B)对步骤A)获得的锰基纳米粒进行硅烷羧酸化修饰,得到水溶性具有弛豫性能和可连续发光锰基纳米粒。该锰基纳米粒可用于磁共振和光学双模式成像。
Description
技术领域
本发明属于纳米材料领域,具体涉及一种具有连续发光和弛豫性能的锰基纳米粒及其制备方法。
背景技术
磁共振成像与荧光成像的联合应用可有效提高肿瘤诊断的准确性,但通常荧光成像只发射单一颜色光谱,在应用于各种生物成像、生物标记时受到限制。如何提供一种既能连续发光又具有弛豫性能,能够作为双模式探针应用于磁共振与荧光双模式成像的纳米粒,成为业界需要解决的技术难题。
发明内容
有鉴于此,本发明的主要目的在于提供一种具行连续发光和弛豫性能的锰基纳米粒及其制备方法,以解决上述技术问题中的至少之一。
为实现上述目的,作为本发明的一个方而,本发明提供了一种具行连续发光和弛豫性能的锰基纳米粒的制备方法,包括以下步骤:
以油酸锰为前驱体,热分解得到锰基纳米粒;
对上述步骤的产物进行后处理,得到所述具有弛豫性能和可连续发光的锰基纳米粒。
其中,所述后处理步骤具体包括:
对前一步骤的产物用有机溶剂洗涤离心,得到黄色油层,对所述黄色油层进行多次洗涤离心,得到沉淀物;所述有机溶剂为乙醇或丙酮;
对离心后得到的沉淀物用正己烷溶解,得到所述油酸包裹的锰基纳米粒。
其中,所述后处理步骤之后还包括以下步骤:
加入硅烷羧酸化试剂,使所述锰基纳米粒中的油酸被替换而形成水溶性纳米粒;所述硅烷羧酸化步骤具体包括:
将油酸包裹的锰基纳米粒溶于甲苯、冰醋酸混合液中,与硅烷羧酸化试剂在60-80℃反应24-48h,其中纳米粒的质量与硅烷羧酸试剂的体积比为100mg∶0.5-2mL。
其中,所述油酸锰前驱体进一步通过如下步骤配制:
将氯化锰与油酸钠在水、无水乙醇、正己烷的混合溶剂中70℃油浴4h,洗涤干燥;
其中,所述水、无水乙醇、正己烷的混合溶剂中,三者的体积比为3∶4∶7;氯化锰与油酸钠的摩尔比为1∶3~5。
其中,在热分解得到锰基纳米粒的步骤中,热分解中所用的溶剂为十八烯或油胺。
其中,热分解温度为100~340℃,热分解反应时间为1~4h。
作为本发明的另一个方而,本发明还提供了一种根据如上所述的制备方法制备得到的锰基纳米粒。
其中,所述锰基纳米粒用于光学和磁共振成像。
其中,所述锰基纳米粒在不同激发光下连续发光。
基于上述技术方案可知,本发明的锰基纳米粒的制备方法具有工艺简单、产率高等特点,且所制备的锰基纳米粒既能连续发光,又具有弛豫性能,有望作为一类新型探针应用于磁共振与光学双模式成像。
附图说明
图1为本发明的锰基纳米粒的透射电镜图;
图2为本发明的锰基纳米粒在不同波长激发光激发下的荧光发射光谱图;
图3为本发明的锰基纳米粒在不同波长激发光激发下的色度图;
图4为本发明的锰基纳米粒的弛豫率测定曲线图;
图5a-5d为本发明的锰基纳米粒用于C6胶质瘤细胞激光共聚焦成像图,其中图5a和图5b分别是405nm和458nm激发下的激光共聚焦图,图5c是C6胶质瘤细胞明场的激光共聚焦图,图5d是叠加图;
图6a、图6b分别为本发明的锰基纳米粒用于脑胶质瘤模型小鼠脑部之前和5min后的磁共振成像图。
具体实施方式
为使本发明的目的、技术方案和优点更加清楚明白,以下结合具体实施例,并参照附图,对本发明作进一步的详细说明。
本发明公开了一种锰基纳米粒的制备方法,其首先制备前驱体油酸锰,再进行热分解,对反应物进行离心后所得的黄色油层进行后处理得到锰基纳米粒。
具体地,本发明的锰基纳米粒的制备方法,主要包括以下步骤:
以油酸锰为前驱体,热分解得到锰基纳米粒;
对上述步骤的产物进行后处理,得到锰基纳米粒溶液。
其中,后处理步骤包括:
加入有机溶剂洗涤离心,得到黄色油层,对该黄色油层进行多次洗涤离心得到沉淀物;该有机溶剂例如为乙醇或丙酮;
对离心后所得沉淀物用正己烷溶解,得到油酸包裹的锰基纳米粒。
其中,后处理步骤之后还包括以下步骤:
硅烷羧酸化,使其替代油酸变成水溶性纳米粒,其具体步骤例如包括:
将一定量的油酸包裹的锰基纳米粒溶于甲苯、冰醋酸混合液中,与硅烷羧酸化试剂在60-80℃反应24-48h,其中纳米粒的质量与硅烷羧酸试剂的体积比为100mg∶0.5-2mL。
其中,上述油酸锰前驱体优选通过如下步骤配制:
将锰盐与油酸盐以不同比例,在水、无水乙醇、正己烷三者的混合溶剂中65-75℃油浴3-5h,洗涤干燥;其中,锰盐例如为氯化锰、硝酸锰等溶于水的盐类,油酸盐例如为油酸钾、油酸钠等;水、无水乙醇、正己烷三者的混合溶剂中,三者的体积比优选为3∶4∶7。氯化锰与油酸钠的摩尔比例如为1∶3~5。
在上述热分解得到锰基纳米粒的步骤中,热分解中所用的溶剂例如为十八烯或油胺。热分解温度为100~340℃,热分解反应时间为1~4h。
本发明还公开了一种通过上述方法制备得到的锰基纳米粒,其具有连续发光性能和弛豫性能,可用于光学和磁共振成像。
下面结合具体实施例进一步说明本发明的技术方案。
实施例1
1、制备油酸锰前驱体
将氯化锰与油酸钠在水、无水乙醇、正己烷的混合溶剂中70℃油浴4h,有机层用水洗三遍,旋干,得油酸锰;其中,水、无水乙醇、正己烷的混合溶剂中,三者的体积比为3∶4∶7,氯化锰与油酸钠的摩尔比为1∶3。
2、热分解制备锰基纳米粒:
在三口瓶中加入2.46g油酸锰、50mL十八烯,进行热分解,真空条件下100℃30min,后在氮气保护下200℃反应20min,再升至280℃反应10min,最后在310℃反应10min,冷却至室温;反应液加适量乙醇进行离心(7500rpm,10min),得到上层清液、中间黄色油层与下层黑色沉淀,将中间黄色油层单独分离,加乙醇进行洗涤、离心(7500rpm,10min),直至沉淀完全。取沉淀,加适量正己烷溶解,得到油酸包裹的锰基纳米粒。在电镜下观察,该锰基纳米粒为球形,大小均一
3、硅烷羧酸修饰得到水溶性锰基纳米粒:
100mg油酸包裹的锰基纳米粒与60mL甲苯、60μL冰醋酸超声15min,再加入1mL硅烷羧酸,70℃油浴反应36小时收集反应液中的沉淀,分别用甲苯洗三次,甲醇洗三次后,加适量水进行溶解,转移至透析袋(Mw=8000-12000)中透析24h,后将液体冻干,得到硅烷羧酸修饰的水溶性锰基纳米粒粉末。
实施例2
具体步骤同实施例1,区别仅在于其中的油酸锰前驱体通过如下步骤制备:
将氯化锰与油酸钾在水、无水乙醇、正己烷的混合溶剂中65℃油浴5h,有机层用水洗三遍,旋干,得油酸锰;其中,水、无水乙醇、正己烷的混合溶剂中,三者的体积比为3∶4∶7,氯化锰与油酸钠的摩尔比为1∶4。在电镜下观察,该锰基纳米粒粉末外表稍有不规则,大小形貌不很均一,但其它性能均能合乎要求。
实施例3
具体步骤同实施例1,区别仅在于其中的油酸锰前驱体通过如下步骤制备:
将硝酸锰与油酸钠在水、无水乙醇、正己烷的混合溶剂中75℃油浴3h,有机层用水洗三遍,旋干,得油酸锰;氯化锰与油酸钠的摩尔比为1∶5。在电镜下观察,该锰基纳米粒粉末外表很不规则,大小形貌不均一,但其它性能均能合乎要求。
实施例4
具体步骤同实施例1,区别仅在于其中的热分解制备锰基纳米粒的步骤如下:
在三口瓶中加入2.46g油酸锰、50mL十八烯,进行热分解,真空条件下100℃30min,后在氮气保护下200℃反应20min,再升至280℃反应30min,最后在310℃反应60min,冷却至室温;洗涤步骤同实施例1。
在电镜下观察,该锰基纳米粒为球形,形貌较不均一,其它性能也均合乎要求。
实施例5
具体步骤同实施例1,区别仅在于其中的硅烷羧酸修饰得到水溶性锰基纳米粒的步骤如下:
100mg油酸包裹的锰基纳米粒与60mL甲苯、60μL冰醋酸超声15min,再加入0.6mL硅烷羧酸,70℃油浴反应48小时收集反应液中的沉淀,分别用甲苯洗三次,甲醇洗三次后,加适量水进行溶解,转移至透析袋(Mw=8000-12000)中透析24h,后将液体冻干,得到硅烷羧酸修饰的水溶性锰基纳米粒粉末,其性能也均能合乎要求。
性能测试-荧光发射光谱和色度图
1)将实施例1得到的锰基纳米粒配制成1mg/mL的水溶液;
2)测该溶液分别在360nm、380nm、400nm、420nm、440nm、460nm、480nm、500nm、520nm、540nm、560nm、580nm及600nm波长激发光激发下的荧光发射光谱谱图及相应色度图(结果参见图2及图3)。
性能测试-弛豫率
1)将实施例1得到的水溶性纳米粒配制成锰含量为0.25mg/mL、0.125mg/mL、0.0625mg/mL、0.03125mg/mL的溶液;
2)在7T磁共振成像仪上分别进行纯水和不同浓度锰基纳米粒溶液的MR T1扫描,测定弛豫率(结果见图4)。
性能测试-激光共聚焦图
1)在培养皿中接种C6胶质瘤细胞,并于37℃、5%CO2培养箱中培养;
2)培养24h后,吸去上清液,加入含有实施例1得到的锰基纳米粒基的培养基,在37℃、5%CO2培养箱中共孵育12h;
3)取出培养皿,用PBS(磷酸盐缓冲溶液)清洗,最后加入少量PBS;
4)在激光共聚焦显微镜下(405nm)观察细胞成像(结果见图5a-5d),锰基纳米粒标记的细胞在405nm激发光激发下发出蓝色荧光,在458nm激发光激发下发出绿色荧光。其中图5a和图5b分别是405nm和458nm激发下的激光共聚焦图,图5c是C6胶质瘤细胞明场的激光共聚焦图,图5d是叠加图。
性能测试-磁共振成像
1)以7.6mg Mn每公斤小鼠剂量将实施例1得到的锰基纳米粒通过尾静脉注射入脑胶质瘤模型小鼠体内;
2)进行脑部磁共振成像(结果见图6a、图6b),给药后5min可见肿瘤部位具有磁共振T1成像增强效果。
以上所述的具体实施例,对本发明的目的、技术方案和有益效果进行了进一步详细说明,应理解的是,以上所述仅为本发明的具体实施例而已,并不用于限制本发明,凡在本发明的精神和原则之内,所做的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (9)
1.一种具有弛豫性能和可连续发光锰基纳米粒的制备方法,其特征在于,包括以下步骤:
以油酸锰为前驱体,热分解得到锰基纳米粒;
对上述步骤的产物进行后处理,得到所述具有弛豫性能和可连续发光的锰基纳米粒。
2.根据权利要求1所述的方法,其中所述后处理步骤具体包括:
对前一步骤的产物用有机溶剂洗涤离心,得到黄色油层,对所述黄色油层进行多次洗涤离心,得到沉淀物;所述有机溶剂为乙醇或丙酮;
对离心后得到的沉淀物用正己烷溶解,得到所述油酸包裹的锰基纳米粒。
3.根据权利要求1所述的方法,其中所述后处理步骤之后还包括以下步骤:
加入硅烷羧酸化试剂,使所述锰基纳米粒中的油酸被替换而形成水溶性纳米粒;所述硅烷羧酸化步骤具体包括:
将油酸包裹的锰基纳米粒溶于甲苯、冰醋酸混合液中,与硅烷羧酸化试剂在60-80℃反应24-48h,其中纳米粒的质量与硅烷羧酸试剂的体积比为100mg∶0.5-2mL。
4.根据权利要求1所述的方法,其中所述油酸锰前驱体进一步通过如下步骤配制:
将氯化锰与油酸钠在水、无水乙醇、正己烷的混合溶剂中70℃油浴4h,洗涤干燥;
其中,所述水、无水乙醇、正己烷的混合溶剂中,三者的体积比为3∶4∶7;氯化锰与油酸钠的摩尔比为1∶3~5。
5.根据权利要求1所述的方法,其中在热分解得到锰基纳米粒的步骤中,热分解中所用的溶剂为十八烯或油胺。
6.根据权利要求1所述的方法,其中热分解温度为100~340℃,热分解反应时间为1~4h。
7.一种根据权利要求1至6任意一项所述的制备方法制备得到的锰基纳米粒。
8.根据权利要求7所述的锰基纳米粒,所述锰基纳米粒用于光学和磁共振成像。
9.根据权利要求7所述的锰基纳米粒,所述锰基纳米粒在不同激发光下连续发光。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103495186A (zh) * | 2013-09-27 | 2014-01-08 | 首都医科大学 | 一种对脑胶质瘤特异靶向的氧化锰纳米粒造影剂 |
US20150361334A1 (en) * | 2014-06-16 | 2015-12-17 | Postech Academy-Industry Foundation | Process for preparing carbon quantum dots using emulsion |
CN105797175A (zh) * | 2016-03-31 | 2016-07-27 | 福州大学 | PAAsMnO(OH)-RGD药物释放载体的制备方法及应用 |
-
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103495186A (zh) * | 2013-09-27 | 2014-01-08 | 首都医科大学 | 一种对脑胶质瘤特异靶向的氧化锰纳米粒造影剂 |
US20150361334A1 (en) * | 2014-06-16 | 2015-12-17 | Postech Academy-Industry Foundation | Process for preparing carbon quantum dots using emulsion |
CN105797175A (zh) * | 2016-03-31 | 2016-07-27 | 福州大学 | PAAsMnO(OH)-RGD药物释放载体的制备方法及应用 |
Non-Patent Citations (1)
Title |
---|
BAOJIN MA, ET AL.: "Prolonged fluorescence lifetime of carbon quantum dots by combining with hydroxyapatite nanorods for bio-applications", 《NANOSCALE》 * |
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