CN113577313A - 一种靶向识别型超支化聚硅氧烷荧光材料及制备方法和使用方法 - Google Patents
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Abstract
本发明涉及一种靶向识别型超支化聚硅氧烷荧光材料及制备方法和使用方法,以3‑氨丙基三乙氧基硅烷与二元醇为原料通过亲核取代缩聚反应合成超支化聚硅氧烷,再对其接枝半胱氨酸,最后接枝VEGF核酸适配体,从而得到靶向识别型超支化聚硅氧烷荧光材料。通过该方法合成的靶向识别型超支化聚硅氧烷荧光材料可发射明亮的荧光,具有良好的生物相容性,低生物毒性。并且,由于接枝了VEGF核酸适配体,其可以与癌细胞表面过度表达的膜蛋白特异性结合,使其能够靶向特异识别癌细胞,在特定的癌细胞表面积累,并通过内吞作用进入癌细胞内部,实现靶向癌细胞成像,同时,结合其良好的药物负载能力实现靶向药物控释,进而实现靶向药物运输和体内示踪一体化。
Description
技术领域
本发明属于高分子发光材料领域,涉及一种靶向识别型超支化聚硅氧烷荧光材料及制备方法和使用方法。
背景技术
靶向识别在癌症治疗中有重要意义,赋予荧光探针以靶向性,可以使其在在特定的肿瘤内积累,提高荧光成像的精确性。此外,具有靶向性的药物输送系统可以使药物输送体系在适应机体内复杂多变的生理环境的同时,在特定部位提高药物浓度,实现高效、精准的特异性识别,减少对正常细胞的影响。因此,构建具有靶向性的可视化药物输送体系,实现高效、精准的靶向特异性癌细胞成像及可视化药物控释,具有极大应用前景。采用共价/非共价作用将荧光团与药物载体相连接是构建可视化药物载体最常用的途径。然而,常用的荧光团多具有稠环芳烃结构,易发生聚集导致猝灭(ACQ)现象,并且生物毒性高,生物相容性差,严重阻碍了其发展和应用。因此,开发克服ACQ缺点且具有良好生物相容性的新型可视化药物载体,并赋予其靶向识别特性,具有重要意义。
传统的共轭型聚集诱导发光(AIE)材料虽然克服了ACQ的难题,并且已有对其进行靶向功能化的探索,但是该类材料仍存在生物毒性高,生物相容性差的缺点,并且该类材料需要和药物载体结合才能用于药物负载[Analytical Chemistry,2018,90(2):1063-1067;Acs Applied Materials&Interfaces,2014,6(7):5212-20]。而非共轭型AIE材料因不含大π共轭基元而在生物相容性、环境友好性等方面具有极大的优势,有望用作新型可视化药物载体[化学学报,2013,71(007):979-990]。超支化聚硅氧烷(HBPSi)作为一种非共轭AIE荧光聚合物,其分子结构中仅含氨基、羟基、酯基、羧基等助色团,不含大π共轭基元,具有优异的生物相容性,其可用于细胞成像以及药物控释可视化等领域,但缺乏靶向识别癌细胞的功能,限制了其在细胞成像和药物控释等领域的应用[Journal of Hazardous Materials,2015,287(0):259-267;Macromolecular Rapid Communications,2015,36(8):739-743;Macromolecular Rapid Communications,2016,37(2):136-142;Journal of MaterialsChemistry C,2016,4(28):6881-689;Polymer Chemistry,2016,7:3747-3755;RSCAdvances,2016,6(108):106742-106753;Macromolecular Chemistry and Physics,2016,217(10):1185-1190]。
发明内容
要解决的技术问题
为了避免现有技术的不足之处,本发明提出一种靶向识别型超支化聚硅氧烷荧光材料及制备方法和使用方法,通过在超支化聚硅氧烷表面接枝核酸适配体的方式合成具有靶向识别能力的超支化聚硅氧烷药物载体,使其具有良好生物相容性,且能够集靶向运输和体内示踪一体化,在药理研究、局部治疗等领域具有重要的应用价值。
技术方案
一种靶向识别型超支化聚硅氧烷荧光材料,其特征在于以质量比30~50∶1在接枝了半胱氨酸的超支化聚硅氧烷表面接枝血管内皮生长因子VEGF核酸适配体,得到靶向识别型超支化聚硅氧烷荧光材料;所述接枝了半胱氨酸的超支化聚硅氧烷是超支化聚硅氧烷与半胱氨酸按质量比为6~10∶1合成;所述超支化硅氧烷是以摩尔比为1∶1~2.5的3-氨丙基三乙氧基硅烷与二元醇为原料合成得到超支化硅氧烷。
所述二元醇包括但不限于二乙醇胺、N-甲基二乙醇胺、1,4-丁二醇、1,6-己二醇、丙二醇。
一种制备所述靶向识别型超支化聚硅氧烷荧光材料的方法,其特征在于步骤如下:
步骤1:将3-氨丙基三乙氧基硅烷与二元醇按摩尔比为1∶1~2.5混合,在氮气保护下,升温至90~120℃,保持10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到含氨基的超支化聚硅氧烷;
步骤2:将超支化聚硅氧烷与半胱氨酸按质量比为6~10∶1混合,升温至60~80℃,反应10~60min后固体溶解,继续反应24~48h后降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷;
步骤3:最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为30~50∶1混合,在氮气保护下,降温至0~10℃,反应24~48h,然后升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
一种所述靶向识别型超支化聚硅氧烷荧光材料的用途,其特征在于:所述靶向识别型超支化聚硅氧烷荧光材料,接枝的VEGF核酸适配体与癌细胞表面过度表达的膜蛋白特异性结合,使其能够靶向特异识别癌细胞,在特定的癌细胞表面积累,并通过内吞作用进入癌细胞内部,实现靶向癌细胞成像,同时,结合其良好的药物负载能力实现靶向药物控释,进而实现靶向药物运输和体内示踪一体化。
有益效果
本发明提出的一种靶向识别型超支化聚硅氧烷荧光材料及制备方法和使用方法,以3-氨丙基三乙氧基硅烷与二元醇为原料通过亲核取代缩聚反应合成超支化聚硅氧烷,再对其接枝半胱氨酸,最后接枝VEGF核酸适配体,从而得到靶向识别型超支化聚硅氧烷荧光材料。通过该方法合成的靶向识别型超支化聚硅氧烷荧光材料可发射明亮的荧光,具有良好的生物相容性,低生物毒性。并且,由于接枝了VEGF核酸适配体,其可以与癌细胞表面过度表达的膜蛋白特异性结合,使其能够靶向特异识别癌细胞,在特定的癌细胞表面积累,并通过内吞作用进入癌细胞内部,实现靶向癌细胞成像,同时,结合其良好的药物负载能力实现靶向药物控释,进而实现靶向药物运输和体内示踪一体化。
本发明通过接枝血管内皮生长因子(Vascular endothelial growth factor,VEGF)核酸适配体,利用VEGF核酸适配体与癌细胞表面过度表达的膜蛋白的特异性结合能力赋予超支化聚硅氧烷靶向识别特性。其不仅具有优异的生物相容性,低的细胞毒性,还可以实现靶向癌细胞成像和可视化药物控释,进而实现靶向药物运输和体内示踪一体化。
附图说明
图1:靶向识别型超支化聚硅氧烷荧光材料的合成原理图。3-氨丙基三乙氧基硅烷与二元醇(包括但不限于二乙醇胺、N-甲基二乙醇胺、1,4-丁二醇、1,6-己二醇、丙二醇),采用亲核取代缩聚反应合成超支化硅氧烷,再对其接枝半胱氨酸,最后接枝VEGF核酸适配体,从而得到靶向识别型超支化聚硅氧烷荧光材料。
图2:靶向识别型的超支化聚硅氧烷荧光材料的靶向识别及药物控释机理图。靶向识别型超支化聚硅氧烷荧光材料表面的VEGF核酸适配体可以与癌细胞表面过度表达的膜蛋白特异性结合,从而靶向特异识别癌细胞,在特定的癌细胞表面积累,并通过内吞作用进入癌细胞内部,实现靶向癌细胞成像,同时,可以将其负载的药物阿霉素靶向特异地运送到癌细胞内部,并在癌细胞内部高浓度的谷胱甘肽(GSH)的作用下破坏其自组装结构使得药物释放,由此实现靶向药物控释,进而实现靶向药物运输和体内示踪一体化。
图3:靶向识别型的超支化聚硅氧烷荧光材料的细胞成像。加入靶向识别型超支化聚硅氧烷荧光材料,三阴性乳腺癌细胞(Mda mb 231)的表面会附着更多的荧光分子而发出明显蓝色荧光,而荧光分子在正常细胞(L929)表面无法积累,因此正常细胞无明显荧光,表明该荧光材料对癌细胞有明显的靶向识别能力。
图4:靶向识别型的超支化聚硅氧烷荧光材料的最佳载药浓度。用靶向识别型的超支化聚硅氧烷荧光材料负载药物阿霉素(DOX),随着DOX浓度的增大,该荧光材料的载药量逐渐增加。由于该荧光材料内部的网络状结构有利于DOX被有效包裹在载体内部空腔中,从而使其具有良好的药物负载能力。
具体实施方式
现结合实施例、附图对本发明作进一步描述:
本发明内容中:以3-氨丙基三乙氧基硅烷与二元醇为原料通过亲核取代缩聚反应合成超支化聚硅氧烷,再对其接枝半胱氨酸,最后接枝VEGF核酸适配体,从而得到靶向识别型超支化聚硅氧烷荧光材料。具体的制备方法如下:将3-氨丙基三乙氧基硅烷与二元醇(包括但不限于二乙醇胺、N-甲基二乙醇胺、1,4-丁二醇、1,6-己二醇、丙二醇)按摩尔比为1∶(1~2.5)混合,加入到250mL三口烧瓶中,在氮气保护下,升温至90~120℃,10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到含氨基的超支化聚硅氧烷。之后,将超支化聚硅氧烷与半胱氨酸按质量比为(6~10)∶1混合,加入到100mL单口烧瓶中,升温至60~80℃,反应10~60min后固体溶解,反应24~48h,降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷。最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为(30~50)∶1混合,加入到100mL三口烧瓶中,在氮气保护下,降温至0~10℃,反应24~48h,升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
下面结合实例对本发明进一步说明,本发明包括但不仅限于下述实例。
实例1
将3-氨丙基三乙氧基硅烷与二乙醇胺按摩尔比为1∶(1~2.5)混合,加入到250mL三口烧瓶中,在氮气保护下,升温至90~120℃,10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到超支化聚硅氧烷。之后,将超支化聚硅氧烷与半胱氨酸按质量比为(6~10)∶1混合,加入到100mL单口烧瓶中,升温至60~80℃,反应10~60min后固体溶解,反应24~48h,降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷。最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为(30~50)∶1混合,加入到100mL三口烧瓶中,在氮气保护下,降温至0~10℃,反应24~48h,升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
实例2
将3-氨丙基三乙氧基硅烷与N-甲基二乙醇胺按摩尔比为1:(1~2.5)混合,加入到250mL三口烧瓶中,在氮气保护下,升温至90~120℃,10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到超支化聚硅氧烷。之后,将超支化聚硅氧烷与半胱氨酸按质量比为(6~10):1混合,加入到100mL单口烧瓶中,升温至60~80℃,反应10~60min后固体溶解,反应24~48h,降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷。最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为(30~50):1混合,加入到100mL三口烧瓶中,在氮气保护下,降温至0~10℃,反应24~48h,升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
实例3
将3-氨丙基三乙氧基硅烷与1,4-丁二醇按摩尔比为1:(1~2.5)混合,加入到250mL三口烧瓶中,在氮气保护下,升温至90~120℃,10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到超支化聚硅氧烷。之后,将超支化聚硅氧烷与半胱氨酸按质量比为(6~10):1混合,加入到100mL单口烧瓶中,升温至60~80℃,反应10~60min后固体溶解,反应24~48h,降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷。最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为(30~50):1混合,加入到100mL三口烧瓶中,在氮气保护下,降温至0~10℃,反应24~48h,升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
实例4
将3-氨丙基三乙氧基硅烷与1,6-己二醇按摩尔比为1:(1~2.5)混合,加入到250mL三口烧瓶中,在氮气保护下,升温至90~120℃,10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到超支化聚硅氧烷。之后,将超支化聚硅氧烷与半胱氨酸按质量比为(6~10)∶1混合,加入到100mL单口烧瓶中,升温至60~80℃,反应10~60min后固体溶解,反应24~48h,降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷。最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为(30~50)∶1混合,加入到100mL三口烧瓶中,在氮气保护下,降温至0~10℃,反应24~48h,升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
Claims (4)
1.一种靶向识别型超支化聚硅氧烷荧光材料,其特征在于以质量比30~50∶1在接枝了半胱氨酸的超支化聚硅氧烷表面接枝血管内皮生长因子VEGF核酸适配体,得到靶向识别型超支化聚硅氧烷荧光材料;所述接枝了半胱氨酸的超支化聚硅氧烷是超支化聚硅氧烷与半胱氨酸按质量比为6~10∶1合成;所述超支化硅氧烷是以摩尔比为1∶1~2.5的3-氨丙基三乙氧基硅烷与二元醇为原料合成得到超支化硅氧烷。
2.根据权利要求1所述靶向识别型超支化聚硅氧烷荧光材料,其特征在于:所述二元醇包括但不限于二乙醇胺、N-甲基二乙醇胺、1,4-丁二醇、1,6-己二醇、丙二醇。
3.一种制备权利要求1或2所述靶向识别型超支化聚硅氧烷荧光材料的方法,其特征在于步骤如下:
步骤1:将3-氨丙基三乙氧基硅烷与二元醇按摩尔比为1∶1~2.5混合,在氮气保护下,升温至90~120℃,保持10~60min后,有馏出物产生,反应升温至140~200℃,继续反应至无馏出物产生时反应停止,降至室温即得到含氨基的超支化聚硅氧烷;
步骤2:将超支化聚硅氧烷与半胱氨酸按质量比为6~10∶1混合,升温至60~80℃,反应10~60min后固体溶解,继续反应24~48h后降至室温即得到接枝了半胱氨酸的超支化聚硅氧烷;
步骤3:最后,将接枝了半胱氨酸的超支化聚硅氧烷与VEGF核酸适配体按质量比为30~50∶1混合,在氮气保护下,降温至0~10℃,反应24~48h,然后升至室温即得到靶向识别型超支化聚硅氧烷荧光材料。
4.一种权利要求1所述靶向识别型超支化聚硅氧烷荧光材料的用途,其特征在于:所述靶向识别型超支化聚硅氧烷荧光材料,接枝的VEGF核酸适配体与癌细胞表面过度表达的膜蛋白特异性结合,使其能够靶向特异识别癌细胞,在特定的癌细胞表面积累,并通过内吞作用进入癌细胞内部,实现靶向癌细胞成像,同时,结合其良好的药物负载能力实现靶向药物控释,进而实现靶向药物运输和体内示踪一体化。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115068440A (zh) * | 2022-06-27 | 2022-09-20 | 电子科技大学 | 靶向定位与超声电刺激癌细胞修复的分子机器及制备方法 |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102924722A (zh) * | 2012-08-14 | 2013-02-13 | 西北工业大学 | 一种氨基含量可控的超支化聚硅氧烷制备方法 |
US20170216450A1 (en) * | 2011-05-23 | 2017-08-03 | University Of Massachusetts | Crosslinked polymer nano-assemblies and uses thereof |
CN107129577A (zh) * | 2017-04-13 | 2017-09-05 | 华南理工大学 | 接枝半胱氨酸的聚硅氧烷嵌段共聚物及制备方法与应用 |
US20180016352A1 (en) * | 2015-02-05 | 2018-01-18 | The University Of Queensland | Targeting constructs for delivery of payloads |
CN107753946A (zh) * | 2017-10-23 | 2018-03-06 | 福州大学 | 一种适配体修饰的靶向载药纳米粒及其制备方法与应用 |
CN108659224A (zh) * | 2018-05-29 | 2018-10-16 | 西北工业大学 | 一种超支化聚硅氧烷荧光材料及制备方法 |
WO2021115646A1 (en) * | 2019-12-11 | 2021-06-17 | Empa Eidgenössische Materialprüfungs- Und Forschungsanstalt | Q-t-siloxane-based polymeric materials with low siloxane ring content and method for preparing same |
-
2021
- 2021-07-19 CN CN202110814225.0A patent/CN113577313B/zh active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20170216450A1 (en) * | 2011-05-23 | 2017-08-03 | University Of Massachusetts | Crosslinked polymer nano-assemblies and uses thereof |
CN102924722A (zh) * | 2012-08-14 | 2013-02-13 | 西北工业大学 | 一种氨基含量可控的超支化聚硅氧烷制备方法 |
US20180016352A1 (en) * | 2015-02-05 | 2018-01-18 | The University Of Queensland | Targeting constructs for delivery of payloads |
CN107129577A (zh) * | 2017-04-13 | 2017-09-05 | 华南理工大学 | 接枝半胱氨酸的聚硅氧烷嵌段共聚物及制备方法与应用 |
CN107753946A (zh) * | 2017-10-23 | 2018-03-06 | 福州大学 | 一种适配体修饰的靶向载药纳米粒及其制备方法与应用 |
CN108659224A (zh) * | 2018-05-29 | 2018-10-16 | 西北工业大学 | 一种超支化聚硅氧烷荧光材料及制备方法 |
WO2021115646A1 (en) * | 2019-12-11 | 2021-06-17 | Empa Eidgenössische Materialprüfungs- Und Forschungsanstalt | Q-t-siloxane-based polymeric materials with low siloxane ring content and method for preparing same |
Non-Patent Citations (4)
Title |
---|
SONG NIU,ET AL.: "Water-Soluble Blue Fluorescence-Emitting Hyperbranched Polysiloxanes Simultaneously Containing Hydroxyl and Primary Amine Groups", 《MACROMOL. RAPID COMMUN.》 * |
孙仁凇,等: "壳聚糖纳米粒作为药物递送系统在癌症治疗中的应用", 《中国临床药理学与治疗学》 * |
牛松: "功能性超支化聚硅氧烷的合成及性能研究", 《中国博士学位论文全文数据库工程科技Ⅰ辑》 * |
白天,等: "AIE聚硅氧烷的结构与发光性能研究", 《高分子通报》 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN115068440A (zh) * | 2022-06-27 | 2022-09-20 | 电子科技大学 | 靶向定位与超声电刺激癌细胞修复的分子机器及制备方法 |
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