CN115093548A - 一种自降解共轭聚合物、纳米粒子及其制备方法和应用 - Google Patents
一种自降解共轭聚合物、纳米粒子及其制备方法和应用 Download PDFInfo
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Abstract
本发明公开了一种新型自降解共轭聚合物，并公开了该共轭聚合物及其纳米粒子的制备方法和应用。该自降解共轭聚合物具有优异的近红外一区吸收及近红外二区荧光发射，水溶性纳米粒子由两亲性的F127和该共轭聚合物通过纳米共沉淀方法制备。所制得的纳米粒子发射波长位于近红外二区，可用于近红外二区荧光成像。本发明设计的纳米粒子在激光照射下可以产生大量活性氧及过高热，因此可用于成像引导的肿瘤光动力/光热联合治疗。特别是，共轭聚合物本身产生的活性氧可以导致该共轭聚合物发生降解，可有效降低材料的毒副作用，加快材料在体内的代谢，提高治疗安全性，具有良好的临床应用前景。
Description
技术领域
本发明属于生物光学诊疗领域，更具体地，涉及一种自降解共轭聚合物、纳米粒子及其制备方法和应用。
背景技术
活体荧光成像的质量取决于成像分辨率、穿透深度和灵敏度等因素。然而，生物组织在可见光区或近红外一区(NIR-I，700-900nm)存在不可忽视的光散射，这极大的限制了成像的空间分辨率和穿透深度。此外，可见光具有较高的光子能量，容易激发生物组织的自发荧光，导致成像灵敏度和对比度下降。在第二近红外窗口(NIR-II，1000-1700nm)的荧光成像中，生物体的自发荧光和背景散射被有效的抑制，成像的灵敏度和对比度得到明显的提升。目前为止，NIR-II荧光成像已被用于各种功能性体内生物成像，如血管可视化、血流速度测量以及肿瘤靶向治疗的监测。
光动力疗法(PDT)是一种光照射条件下光敏剂生成有毒的活性氧以破坏癌细胞的治疗方法，具有高重复性、非侵入性和非耐药性等优势；光热疗法(PTT)主要是光热试剂在激光照射后产生的局部过热来杀灭肿瘤细胞，达到肿瘤消融的目的。有机共轭高分子聚合物由于长的π共轭骨架而具有优异的光捕获能力，在NIR-II荧光成像、PDT和PTT方面具有显著的优势。然而，在实际应用中仍存在诸多问题，如不可降解性的共轭聚合物残留引起的毒副作用。如果共轭聚合物在产生活性氧或热起到肿瘤治疗的同时也可以使得共轭聚合物本身发射降解，即自降解，这大大能够降低材料的毒副作用，提高治疗的安全性。基于上述，合理设计一种可自降解的诊疗试剂对于生物医学的发展具有重大的意义。
发明内容
本发明的目的是针对以上不足，提供一种自降解的共轭聚合物，以及基于该共轭聚合物的纳米粒子，并公开了其制备方法，该纳米粒子在激光光照射下可以有效产生NIR-II荧光、活性氧及光热，从而用于NIR-II荧光成像指导的PDT/PTT联合治疗。特别是，共轭聚合物本身产生的活性氧可以导致该共轭聚合物发生降解，可有效降低材料的毒副作用，提高治疗安全性。
为实现上述目的，本发明是通过以下技术方案实现的：
一种自降解共轭聚合物P-F，其结构式如下：
上述自降解共轭聚合物本身产生的活性氧可以导致该共轭聚合物发生降解。
本发明还提供了上述自降解共轭聚合物的制备方法，包括以下步骤：
在氮气保护下，将(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)、(E)-6,6'-二溴-1,1'-双(2-乙基己基)-[3,3'-联二亚吲哚]-2,2'-二酮与钯催化剂混合，加入超干甲苯，100℃回流反应24h。
上述自降解共轭聚合物的合成路线如下：
优选的，上述制备方法中，所述(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)与E)-6,6'-二溴-1,1'-双(2-乙基己基)-[3,3'-联二亚吲哚]-2,2'-二酮的摩尔比为1:1，(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)与钯催化剂的摩尔比为1:0.05。
本发明还提供了一种上述自降解共轭聚合物的纳米粒子，基于式1所述的自降解共轭聚合物P-F，利用两亲性聚合物F127及纳米共沉淀法制备得到的。
上述自降解共轭聚合物的纳米粒子，在水溶液中，最大吸收波长在645nm，最大发射波长在938nm，可用于NIR-II的活体成像。
上述自降解共轭聚合物的纳米粒子，在水溶液中，激光照射后可以产生过高热，即具有光热性质；
上述自降解共轭聚合物的纳米粒子，在水溶液中，激光照射后可以产生活性氧，即具有光动力性质。
上述自降解共轭聚合物的纳米粒子，共轭聚合物本身产生的活性氧可以导致该共轭聚合物发生降解，可有效降低材料的毒副作用，提高治疗安全性。
本发明还提供了上述自降解共轭聚合物的纳米粒子的制备方法，包括以下步骤：
将式1所述的自降解共轭聚合物P-F与两亲性聚合物F127溶于四氢呋喃中，超声溶解得混合溶液；
将上述混合溶液于超声下加入去离子水中，继续超声5min；
去除溶液中的四氢呋喃，制得自降解共轭聚合物的纳米粒子溶液。
优选的，上述制备方法中，所述自降解共轭聚合物与两亲性聚合物F127的质量比为1:20。
本发明还提供了一种上述的自降解共轭聚合物在制备NIR-II荧光成像造影剂中的应用，是指使用其纳米粒子水溶液制备NIR-II荧光成像造影剂。
本发明还提供了一种上述的自降解共轭聚合物在制备NIR-II荧光成像指导的PDT/PTT联合治疗试剂中的应用，是指使用其纳米粒子制备备NIR-II荧光成像指导的PDT/PTT联合治疗试剂。
与现有技术相比，本发明的有益效果为：
本发明合成了一种自降解共轭聚合物，本身产生的活性氧可以导致该共轭聚合物发生降解，可有效降低材料的毒副作用，提高治疗安全性。
本发明所述自降解共轭聚合物的纳米粒子，其发射波长位于NIR-II范围，因此可以进行NIR-II区的荧光成像。本发明的自降解共轭聚合物纳米粒子在激光照射下可产生光热和光动力性能，因此可应用于肿瘤联合治疗，显著提高治疗效果。本发明设计的共轭聚合物本身产生的活性氧可以导致该共轭聚合物发生降解，减弱了潜在的生物毒性，具有较好的临床应用前景。
附图说明
图1为本发明实施例所述的自降解共轭聚合物P-F的氢谱图；
图2为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs在水中的吸收和发射图谱；
图3为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs不同浓度下随激光照射的升温曲线；
图4为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs与DPBF混合后，在激光照射下414nm处吸收强度随时间的变化曲线；
图5为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs水溶液经激光照射后的吸收光谱变化；
图6为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs与Vc共混经激光照射后的最大吸收折线图；
图7为本发明实施例所述的自降解共轭聚合物纳米粒子P-F NPs经尾静脉注射后小鼠皮下肿瘤的荧光成像图。
具体实施方式
下面将结合附图和具体实施例更详细地描述本发明的优选实施方式。
本发明的实施例所使用的试剂皆为市购，所使用的仪器分别为：
近红外二窗荧光成像仪：NIRvana 640-Princeton instrument
红外热成像仪：FLIR E50
激光器：MDL-IH-730-2W-PSU-II-LED
实施例1
一种自降解共轭聚合物P-F，其结构式如式1所示：
上述自降解共轭聚合物的合成路线如下：
其具体的合成步骤如下：
称取(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)(化合物1，0.20g，0.27mmol)，(E)-6,6'-二溴-1,1'-双(2-乙基己基)-[3,3'-联二亚吲哚]-2,2'-二酮(化合物2，0.17g，0.27mmol)，四(三苯基膦)钯(0.031g，0.027mmol)置于50mL的Schlenk反应管中；氮气保护下加入5mL甲苯，并在100℃油浴锅中回流反应24小时。反应完毕后，将反应液滴入200mL甲醇沉降，抽滤，洗涤数次，得到黑色固体粉末P-F0.30g(产率81％)，其氢谱图如图1所示。
实施例2
1.一种实施例1所述的自降解共轭聚合物的纳米粒子，其制备方法如下：
步骤一：称取实施例1所制备的P-F 0.5mg，10mg的F127溶于1mL四氢呋喃中，超声溶解，至溶液澄清；
步骤二：超声下将上述混合物溶液通过移液枪快速加入5mL去离子水中，并继续超声5min，得到蓝色的纳米粒子水溶液；
步骤三：将含有四氢呋喃的纳米粒子溶液在通风橱搅拌过夜，以除去残留的四氢呋喃，得到纳米粒子溶液P-F NPs；所得纳米粒子溶液通过0.22μm的微孔滤膜过滤，超滤离心浓缩至1mg/mL，储存4℃冰箱备用。
2.吸收和发射光谱测试
将实施例2制得的自降解共轭聚合物纳米粒子分散在水溶液中，稀释至10-5M用以光谱测试，其在水溶液中的吸收和发射光谱如图2所示，纳米粒子的最大吸收峰在645nm，最大发射峰在938nm，表明该纳米粒子可用于近红外二区成像。
3.光热性能的测试
将实施例2制得的自降解共轭聚合物纳米粒子水溶液分别稀释至150、120、90、60和30μg/mL，放置于200μL的离心管中，使用730nm激光照射离心管，并通过热成像仪记录实时的升温情况。在不同浓度时随激光照射时间的升温曲线如图3所示，从图中可以发现，随着纳米粒子浓度的升高，温度上升明显加快，表明纳米粒子具有显著的光热性质。
4.光动力测试
将实施例2制得的自降解共轭聚合物纳米粒子和DPBF混合后用于吸收测试。具体的，纳米粒子在730nm处的吸收在0.2左右，DPBF在414nm处的吸收强度在1.2左右，光照10min进行一次测试。其吸收强度随时间的变化曲线如图4所示，从图中可以发现，激光照射后DPBF的吸收发生明显的降低，且随着激光功率密度的增强，DPBF的吸收下降幅度加快，表明纳米粒子的光动力效果具有激光功率依赖性。
5.降解测试
将实施例2制得的自降解共轭聚合物纳米粒子水溶液分别稀释至100μg/mL，通过730nm激光器照射，并通过吸收光谱分析纳米粒子的降解情况。其照射后的吸收光谱如图5所示，从图中可以发现，随着照射时间的增长，纳米粒子的吸收强度逐渐降低，说明经过光照后共轭聚合物发生了降解。加入活性氧抑制剂后发现纳米粒子吸收下降速率明显降低，表明是由共轭聚合物本身产生的活性氧导致聚合物降解。
将实施例2制得的自降解共轭聚合物纳米粒子与ROS抑制剂Vc共混之后，经730nm激光器照射。其照射后的吸收最高峰折线图如图6所示，从图中可以发现，当加入抑制剂后纳米粒子的降解速度得到了有效的降低，表明ROS的产生是促使其降解的原因。
5.荧光成像应用
将实施例2制得的自降解共轭聚合物纳米粒子水溶液浓缩至1mg/mL，然后对荷瘤小鼠进行尾静脉注射，通过二区成像仪获取纳米粒子在肿瘤处的富集情况。所述自降解共轭聚合物纳米粒子P-F NPs经尾静脉注射后小鼠皮下肿瘤的NIR-II荧光成像结果如图7所示，从图中明显的观察到纳米粒子富集在小鼠腋下的肿瘤，表明纳米粒子可以精准的进行肿瘤的识别。
以上已经描述了本发明的各实施例，上述说明是示例性的，并非穷尽性的，并且也不限于所披露的各实施例。在不偏离所说明的各实施例的范围和技术原理的情况下，对于本技术领域的普通技术人员来说许多修改和变更都是显而易见的，这些修改和变更也应视为本发明的保护范围。
Claims (10)
1.一种自降解共轭聚合物，其特征在于，所述自降解共轭聚合物为P-F，其结构式如下：
2.一种权利要求1所述的自降解共轭聚合物的制备方法，其特征在于，包括以下步骤：
在氮气保护下，将(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)、(E)-6,6'-二溴-1,1'-双(2-乙基己基)-[3,3'-联二亚吲哚]-2,2'-二酮与钯催化剂混合，加入超干甲苯，100℃回流反应24h。
3.根据权利要求2所述的自降解共轭聚合物的制备方法，其特征在于，所述(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)与E)-6,6'-二溴-1,1'-双(2-乙基己基)-[3,3'-联二亚吲哚]-2,2'-二酮的摩尔比为1:1。
4.根据权利要求2所述的自降解共轭聚合物的制备方法，其特征在于，所述(4,4-二辛基-4H-环戊二烯[2,1-b:3,4-b']二噻吩-2,6-二基)双(三甲基锡烷)与钯催化剂的摩尔比为1:0.05。
5.一种权利要求1或2所述的自降解共轭聚合物的纳米粒子，其特征在于，是基于式1所述的自降解共轭聚合物P-F，利用两亲性聚合物F127及纳米共沉淀法制备得到的。
6.根据权利要求5所述的自降解共轭聚合物的纳米粒子，其特征在于，所述自降解共轭聚合物的纳米粒子在水溶液中，最大吸收波长在645nm，最大发射波长在938nm。
7.一种权利要求5所述的自降解共轭聚合物的纳米粒子的制备方法，其特征在于，包括以下步骤：
将式1所述的自降解共轭聚合物P-F与两亲性聚合物F127溶于四氢呋喃中，超声溶解得混合溶液；
将上述混合溶液于超声下加入去离子水中，继续超声5min；
去除溶液中的四氢呋喃，制得自降解共轭聚合物的纳米粒子溶液。
8.根据权利要求7所述的自降解共轭聚合物的纳米粒子的制备方法，其特征在于，所述自降解共轭聚合物与两亲性聚合物F127的质量比为1:20。
9.一种权利要求1所述的自降解共轭聚合物在制备NIR-II荧光成像造影剂中的应用。
10.一种权利要求1所述的自降解共轭聚合物在制备NIR-II荧光成像指导的PDT/PTT联合治疗试剂中的应用。
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Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120128782A1 (en) * | 2009-05-15 | 2012-05-24 | The Johns Hopkins University | Multicomponent Degradable Cationic Polymers |
| JP2012243911A (ja) * | 2011-05-18 | 2012-12-10 | Konica Minolta Holdings Inc | 有機光電変換素子およびその製造方法 |
| CN103159926A (zh) * | 2011-12-09 | 2013-06-19 | 海洋王照明科技股份有限公司 | 异靛基共聚物有机半导体材料及其制备方法和应用 |
| US20130220415A1 (en) * | 2010-11-25 | 2013-08-29 | Ocean's King Lighting Science & Technology Co., Ltd. | Conjugated polymer containing isoindigo units, preparation method and use thereof |
| US20150175747A1 (en) * | 2012-07-25 | 2015-06-25 | National University Of Singapore | Highly Emissive Far-Red/Near-Infrared Fluorescent Conjugated Polymer-Based Nanoparticles |
| CN105732957A (zh) * | 2016-04-05 | 2016-07-06 | 中国科学院大学 | 基于异靛青的a-a型共轭聚合物及其制备方法与应用 |
| CN106103436A (zh) * | 2014-03-17 | 2016-11-09 | 默克专利股份有限公司 | 有机半导体化合物 |
| KR20160149477A (ko) * | 2015-06-18 | 2016-12-28 | 연세대학교 산학협력단 | 방향족 화합물을 활용한 전도성 고분자와 무기 나노입자의 복합체 |
| KR20180055555A (ko) * | 2016-11-17 | 2018-05-25 | 충남대학교산학협력단 | 공액화 고분자를 포함하는 나노입자 및 이의 용도 |
| CN108653751A (zh) * | 2017-03-29 | 2018-10-16 | 上海交通大学 | 一种共轭聚合物纳米探针及其制备方法和应用 |
| CN108727567A (zh) * | 2018-05-03 | 2018-11-02 | 上海交通大学 | 引入重原子硒的异靛蓝衍生物共轭聚合物的制备及用途 |
| CN112516337A (zh) * | 2020-12-11 | 2021-03-19 | 南京邮电大学 | 近红外二区有机共轭聚合物荧光探针的制备方法及其应用 |
| CN113087877A (zh) * | 2021-04-06 | 2021-07-09 | 南京邮电大学 | 近红外二区荧光发射水溶性共轭聚合物纳米光疗试剂及其制备方法与应用 |
| CN113956446A (zh) * | 2021-10-12 | 2022-01-21 | 中国科学院大学 | 一种用于治疗乏氧肿瘤的半导体聚合物、制备方法和应用 |
Patent Citations (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20120128782A1 (en) * | 2009-05-15 | 2012-05-24 | The Johns Hopkins University | Multicomponent Degradable Cationic Polymers |
| US20130220415A1 (en) * | 2010-11-25 | 2013-08-29 | Ocean's King Lighting Science & Technology Co., Ltd. | Conjugated polymer containing isoindigo units, preparation method and use thereof |
| JP2012243911A (ja) * | 2011-05-18 | 2012-12-10 | Konica Minolta Holdings Inc | 有機光電変換素子およびその製造方法 |
| CN103159926A (zh) * | 2011-12-09 | 2013-06-19 | 海洋王照明科技股份有限公司 | 异靛基共聚物有机半导体材料及其制备方法和应用 |
| US20150175747A1 (en) * | 2012-07-25 | 2015-06-25 | National University Of Singapore | Highly Emissive Far-Red/Near-Infrared Fluorescent Conjugated Polymer-Based Nanoparticles |
| CN106103436A (zh) * | 2014-03-17 | 2016-11-09 | 默克专利股份有限公司 | 有机半导体化合物 |
| KR20160149477A (ko) * | 2015-06-18 | 2016-12-28 | 연세대학교 산학협력단 | 방향족 화합물을 활용한 전도성 고분자와 무기 나노입자의 복합체 |
| CN105732957A (zh) * | 2016-04-05 | 2016-07-06 | 中国科学院大学 | 基于异靛青的a-a型共轭聚合物及其制备方法与应用 |
| KR20180055555A (ko) * | 2016-11-17 | 2018-05-25 | 충남대학교산학협력단 | 공액화 고분자를 포함하는 나노입자 및 이의 용도 |
| CN108653751A (zh) * | 2017-03-29 | 2018-10-16 | 上海交通大学 | 一种共轭聚合物纳米探针及其制备方法和应用 |
| CN108727567A (zh) * | 2018-05-03 | 2018-11-02 | 上海交通大学 | 引入重原子硒的异靛蓝衍生物共轭聚合物的制备及用途 |
| CN112516337A (zh) * | 2020-12-11 | 2021-03-19 | 南京邮电大学 | 近红外二区有机共轭聚合物荧光探针的制备方法及其应用 |
| CN113087877A (zh) * | 2021-04-06 | 2021-07-09 | 南京邮电大学 | 近红外二区荧光发射水溶性共轭聚合物纳米光疗试剂及其制备方法与应用 |
| CN113956446A (zh) * | 2021-10-12 | 2022-01-21 | 中国科学院大学 | 一种用于治疗乏氧肿瘤的半导体聚合物、制备方法和应用 |
Non-Patent Citations (2)
| Title |
|---|
| HO CC，ET AL: "Synthesis, characterization and photovoltaic properties of poly(cyclopentadithiophene-alt-isoindigo)", POLYMER CHEMISTRY, vol. 4, no. 20, pages 5351 - 5360 * |
| 彭锦雯;杜肖龙;陈妍;孙鹏飞;邓卫星;范曲立;: "近红外二区荧光纳米探针的制备及其在生物成像中的应用", 高分子学报, no. 11, pages 1275 - 1284 * |
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