CN110878050B - 一种可用于双光子光动力治疗的多功能生物探针及其制备方法和用途 - Google Patents
一种可用于双光子光动力治疗的多功能生物探针及其制备方法和用途 Download PDFInfo
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Abstract
Description
技术领域
本发明涉及一种可用于双光子光动力治疗的多功能生物探针及其制备方法和用途,本发明生物探针具有较高的活性氧(ROS)产生效率及双光子效应,又可以同时靶向线粒体及脂滴两种细胞器,从而产生双光子光动力学治疗(TP-PDT)效果。
背景技术
光动力疗法(PDT)是一种非常高效的微创癌症治疗方法,近年来引起广泛关注。例如,可以产生活性氧(ROS)的BODIPY衍生物和卟啉环衍生物等已应用于光动力学治疗,然而,其相对较大的分子量往往导致水溶性较差。此外,具有d8电子构型的Ru(II)和Ir(III)等配合物有较高的光动力学治疗效果,因为其系间窜越较为丰富,较易窜越至T1态,进而容易与氧气作用形成ROS,但是该类化合物在细胞中通常有较高的暗毒性和较低的代谢率。
值得注意的是,大多数已报道的光动力学治疗探针被限制在靶向单一细胞器。这大大限制了治疗的时效性,因为细胞死亡,如自噬细胞死亡(ACD)、凋亡或坏死涉及多个细胞器(如溶酶体,内质网等)的损害和作用。因此,以光动力学治疗为目标的多细胞器靶向分子将有利于诱导更强的细胞光毒性。
双光子激光相较于单光子激光有波长更长、能量更低、组织穿透能力更强等优势,其本身对生物体的损伤更小,双光子光动力学治疗可以在治疗效果好的情况下对正常组织细胞损伤小,是一种新型、安全的的肿瘤治疗方式,具有广阔的应用前景。
发明内容
本发明提供了一种可用于双光子光动力治疗的多功能生物探针及其制备方法和用途,通过分子设计合成了一种具有优异的双光子活性、较低暗毒性及较高光毒性,并能同时靶向线粒体及脂滴两种细胞器的小分子U-TsO,鉴于U-TsO具有优异的综合性能,可作为一种用于双光子光动力学治疗的生物探针。
本发明可用于双光子光动力治疗的多功能生物探针,简记为U-TsO,其结构式如下:
本发明多功能生物探针的制备方法,包括如下步骤:
在250mL的史莱克瓶中加入干燥的NaH 0.6g(0.024mol),量取重蒸的DMF 15mL将其充分溶解并油封;将U-OH 4.0g(8.65mmol)完全溶解在10mL重蒸的DMF中,缓慢滴加到体系中,常温下搅拌30min,然后称取B1 5.5g(0.02mol)加到反应瓶中,缓慢升温至65℃,反应12h;反应结束后冷却至室温,将反应液倒入大量冰水中,用稀释的HCl溶液调pH值6-7,用二氯甲烷反复萃取,合并萃取液,加入无水硫酸镁干燥,抽滤,蒸干溶剂得油状物,通过柱色谱(乙酸乙酯/石油醚=1:2)得红色油状物U-TsO(4.1g)。产率:71.9%。
本发明合成路线如下:
本发明多功能生物探针的用途,是在双光子光动力治疗的过程中作为生物探针使用。
本发明多功能生物探针能同时靶向线粒体及脂滴两种细胞器,即具有线粒体及脂滴双靶向性。
本发明的有益效果体现在:
1、U-TsO具有良好的刚性平面,有效的限制分子扭转,减少非辐射跃迁的能量损耗,使其具有较高的荧光量子产率(32.24%),更容易产生ROS,导致细胞死亡。如图1、图3所示。
2、U-TsO具有线粒体及脂滴双靶向性,即U-TsO在细胞内可以同时靶向线粒体及脂滴,有利于增强光动力学治疗效果。如图4、图6、图7所示。
3、U-TsO中含有醚氧链,具有较低的暗毒性,其油水分离系数logp为0.87667,容易透过生物膜进入细胞或细胞器。如图1(a)所示。
4、U-TsO具有双光子吸收效应,在680nm波长处双光子荧光信号最强,双光子光动力学治疗相比单光子光动力学治疗,不仅具有高穿透性,而且对正常细胞的损伤更小。如图2、图5所示。
5、U-TsO原料易得,合成简单。不存在类似的可用于双光子光动力治疗的多功能生物染料,具有较强的商业价值。
附图说明
图1(a)U-TsO的光毒性及暗毒性,(b)U-TsO在激光照射下使DCFH-DA的荧光强度增强情况,a图说明U-TsO有很低的暗毒性即细胞毒性低,以及很强的光毒性,b图中DCFH-DA的荧光强度增强,说明U-TsO产生ROS的能力很高,即光毒性强。
图2为U-TsO的双光子吸收截面及其验证。说明U-TsO有较好的双光子效应。
图3为5μM的U-TsO孵育后的细胞在不同时间激光照射下的(a)明场图、(b)DCFH-DA(c)U-TsO的共聚焦荧光图。说明在细胞内U-TsO也具有和体外实验一致的效果,易于产生ROS,进而使DCFH-DA的荧光增强,可用于光动力学治疗。
图4为U-TsO在细胞内与线粒体商业染料及脂滴商业染料的共定位荧光图。从共定位图可以看出,U-TsO在细胞内可以同时靶向线粒体及脂滴。
图5(a)为在一定时间单光子光源激光照射下的U-TsO的光动力学治疗效果图,(b)为一定时间双光子光源激光照射下的U-TsO的光动力学治疗效果图,(c)为细胞明场的局部放大图。说明在一定时间激光照射下,U-TsO孵育过的细胞核膜变形、核冒泡和膜冒泡,为明显的细胞死亡现象,且单双光子都有较为明显的光动力学治疗效果。
图6为U-TsO经光动力学治疗后的荧光图,U-TsO与溶酶体商业染料的共定位图。由图可见,大多数脂滴与溶酶体合并形成自噬溶酶体,说明脂滴中产生ROS诱发细胞自噬细胞死亡。
图7(a)为U-TsO孵育的细胞在光动力学治疗前后线粒体的变化,(b)为线粒体的平均长度。说明在光动力学治疗后线粒体的形态发生明显的变化,由长条状断裂为碎片并膨胀变圆,其平均长度也显著地从5.04μm降至1.36μm。表明U-TsO靶向线粒体并产生光动力学治疗的作用。
具体实施方式
以下通过具体的实施例对本发明技术方案作进一步分析说明。
实施例1:
在250mL的史莱克瓶中加入干燥的NaH 0.6g(0.024mol),量取重蒸的DMF 15mL将其充分溶解并油封;将U-OH 4.0g(8.65mmol)完全溶解在10mL重蒸的DMF中,缓慢滴加到体系中,常温下搅拌30min,然后称取B1 5.5g(0.02mol)加到反应瓶中,缓慢升温至65℃,反应12h;反应结束后冷却至室温,将反应液倒入大量冰水中,用稀释的HCl溶液调pH值6-7,用二氯甲烷反复萃取,合并萃取液,加入无水硫酸镁干燥,抽滤,蒸干溶剂得油状物,通过柱色谱(乙酸乙酯/石油醚=1:2)得红色油状物U-TsO(4.1g)。产率:71.9%。U-TsO:1H NMR(400MHz,d6-DMSO)δppm:8.41(t,J=8.9Hz,2H),7.40(t,J=7.6Hz,2H),7.32(dd,J=13.6,6.6Hz,2H),7.23(dd,J=26.8,7.3Hz,2H),7.04(t,J=8.0Hz,2H),6.80(d,J=8.6Hz,2H),3.65(dd,J=37.3,4.9Hz,4H),3.60(m,4H),3.55(m,22H),2.85(d,J=32.4Hz,8H).13C NMR(100MHz,d6-DMSO)δppm:162.28,149.08,147.77,137.65,134.82,129.63,128.65,127.58,126.78,124.64,122.98,110.92,71.25,69.92,69.81,69.62,58.06,30.72,27.33.ESI-MS(m/z)calcd for C41H50N2O6=666.85,found 667.37([M+H]+).Anal.Calc.for C41H50N2O6:C,73.85;H,7.56;N,4.20;Found:C,73.84;H,7.55;N,4.24.
实施例2:目标分子的生物学研究
1、在96孔板中分别用0、1、5、10和20μM的U-TsO孵育HeLa细胞24小时,并将细胞分为两组,一组无光照,另一组激光照射以观察其光毒性暗毒性;随后用ROS检测试剂2',7'-二氯荧光黄双乙酸盐(DCFH-DA)定量地检测其产生ROS的能力。U-TsO具有较高的光毒性及较低的暗毒性,在用氙灯照射0到10分钟的时间内,DCFH-DA的荧光强度持续且迅速上升,表明其产生ROS的效率较高。
2、用5μM的U-TsO孵育HeLa细胞30分钟,并用线粒体和脂滴的商业染料Mitotracker Deep Red和Nile Red进行共定位确认其靶向位置。然后通过持续的激光照射观察不同时间细胞的形态的变化,在激光照射下细胞核膜、细胞膜均变形表明U-TsO产生ROS导致细胞死亡。
Claims (5)
3.根据权利要求2所述的制备方法,其特征在于:
柱色谱分离的洗脱剂为乙酸乙酯:石油醚=1:2,v/v。
4.一种权利要求1所述的多功能生物探针的用途,其特征在于:
所述多功能生物探针用于制备双光子光动力治疗过程中生物探针的用途。
5.根据权利要求4所述的用途,其特征在于:
所述多功能生物探针能同时靶向线粒体及脂滴两种细胞器,即具有线粒体及脂滴双靶向性。
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102942559A (zh) * | 2012-10-29 | 2013-02-27 | 安徽大学 | 一种柔性醚氧链嘧啶衍生物、其制备方法及其用途 |
WO2015179999A1 (zh) * | 2014-05-30 | 2015-12-03 | 中国科学院大连化学物理研究所 | 细胞色素氧化酶cyp1a的比率型荧光探针底物及其应用 |
CN110194766A (zh) * | 2019-07-04 | 2019-09-03 | 安徽大学 | 一种双通道双光子荧光极性探针及其制备方法和用途 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102942559A (zh) * | 2012-10-29 | 2013-02-27 | 安徽大学 | 一种柔性醚氧链嘧啶衍生物、其制备方法及其用途 |
WO2015179999A1 (zh) * | 2014-05-30 | 2015-12-03 | 中国科学院大连化学物理研究所 | 细胞色素氧化酶cyp1a的比率型荧光探针底物及其应用 |
CN110194766A (zh) * | 2019-07-04 | 2019-09-03 | 安徽大学 | 一种双通道双光子荧光极性探针及其制备方法和用途 |
Non-Patent Citations (3)
Title |
---|
Photodynamic Therapy Directed by Three-Photon Active Rigid Plane Organic Photosensitizer;Hongzhi Cao等;《Adv. Healthcare Mater.》;20201218;第10卷;第2001489(1-9)页 * |
Supramolecular Engineering of Discrete Pt(II)···Pt(II) Interactions for Visible-Light Photocatalysis;Zijian Li等;《ACS Catal.》;20170606;第7卷;第4676-4681页 * |
双光子活性配合物的研究进展;张琼等;《安徽大学学报(自然科学版)》;20170531;第41卷(第3期);第3-10页 * |
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