CN112717132B - 一种具有光声成像性能的缺氧氧化铈的制备及应用 - Google Patents
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Abstract
本发明公开了本发明一种具有光声成像性能的缺氧氧化铈的制备方法，以氧化铈为原料，加入硼氢化钠，在氩气保护下经过600℃高温管式炉反应2小时，得到黑色缺氧氧化铈；将得到的黑色缺氧氧化铈加入研钵，加入二次水进行碾磨，吸取上层液体进行离心洗涤，采用水和乙醇交叉洗涤2‑3次，将洗净的氧化铈溶于水，配置成60 mg/mL的溶液加入寡肽酶切透明质酸1g，在常温下搅拌2h，之后在90℃进行水热反应8h得到CeO2‑x@HA。本发明缺氧氧化铈CeO2‑x@HA作为光敏剂，易于确定注射光敏剂后治疗肿瘤细胞的最佳时间，对于生物体具有良好的生物相容性，且操作简单，成像速度快，成像效果好，而且对于肿瘤具有优异的杀伤效果。
Description
技术领域
本发明涉及氧化铈，具体是一种具有光声成像性能的缺氧氧化铈及其制备方法和应用。
背景技术
光声成像是近年来快速发展的一种基于光声效应的生物医学成像技术。其结合光学成像对比度高以及声学成像穿透力强的特点，在获得高分辨率组织影像的同时，定量分析组织一系列生理参数变化，从而实现功能成像。
研究表明，光声成像技术在众多生物医学领域具有重要的应用价值。作为新兴的生物医学成像模式，光声成像技术凭借优质的成像能力、多样的成像方式以及良好的生物安全性，受到广泛关注。比如乳腺肿瘤显像、泌尿系统成像和心血管系统成像等。
[1] WANG X，PANG Y，KU G，et al．Noninvasive laser-in-duced photoacoustictomography for structural and func-tional in vivo imaging of the brain［J］．Nature Biotechnol-ogy，2003，21(7) :803－806。
[2] YANG D W，XING，D，GU H M，et al． Fast multiele-ment phase-controlledphotoacoustic imaging based onlimited-field-filtered back-projectionalgorithm［J］．Ap-plied Physics Letters，2005，87(19) 。
[3]唐鹤文，杨萌，姜玉新．光声成像分子造影剂［J］．协和医学杂志，2018，9: 358-363。
现有的医学成像手段主要有X射线、电子计算机断层扫描（CT）、磁共振成像（MRI）、单光子发射计算机断层显像（SPECT）、正电子发射型计算机断层显像（PET）、超声成像（Ultrasound）等。但X光检查只能提供平面影像，成像也容易受衣物、首饰甚至过厚的软组织影响。过量的 X 射线照射到生物机体时，重建图像伪影较多还可能造成生物细胞受到破坏。CT成像时，有些部位骨骼伪影太多，影响其周围软组织结构的显示，如颅底部及椎管。MRI成像价格昂贵、成像复杂，容易漏诊小的病状，如肺、肝脏等。不适合急诊或特别危重的病例，因心电监护等急救设备不能进入MRI室。SPECT对人体组织结构及解剖学的变化的分辨不如CT和MRI，对肺、肝、胃肠道肿瘤探查诊断不如CT和MRI。使用PET的单位或其附近的机构必须有生产短半衰期放射性核素的医用回旋加速器故PE检查费高昂。而超声相比之下，价格低廉、简便、迅速、无创、无辐射性、准确、可连续动态及重复扫描，因此易于推广应用，常作为实质脏器及含液器官的首选方法。成像速度快，可适时观察运动脏器并且无辐射性。
发明内容
本发明的目的在于提供一种用于肿瘤治疗以及成像的光敏剂，该光敏剂是具有光声成像性能的缺氧氧化铈，本发明还公开了该缺氧氧化铈的制备方法。
本发明一种具有光声成像性能的缺氧氧化铈的制备方法，以氧化铈为原料，加入硼氢化钠，在氩气保护下经过600℃高温管式炉反应2小时，得到黑色缺氧氧化铈；
将得到的黑色缺氧氧化铈加入研钵，加入二次水进行碾磨，吸取上层液体进行离心洗涤，采用水和乙醇交叉洗涤2-3次，将洗净的氧化铈溶于水，配置成60 mg/mL的溶液加入寡肽酶切透明质酸1g，在常温下搅拌2h，之后在90℃进行水热反应8h得到CeO2-x@HA；
通过红外，紫外以及光声成像等手段对CeO2-x@HA进行鉴定，并通过体外细胞的MTT实验表明得到的CeO2-x@HA具有良好光热效果和光声成像性能。
本发明制备方法中，氧化铈与硼氢化钠的质量比为1:0.8。
采用本发明制备方法得到的缺氧氧化铈CeO2-x@HA，可用于肿瘤治疗以及成像的光敏剂，成像主要是CeO2-x，HA主要是改善材料的水溶性和生物相容性并且起到一个靶向肿瘤CD44受体的作用。用做光敏剂时，通过尾静脉注射的方式将100 µL (3 mg/mL) CeO2-x@HA注入到荷瘤小鼠体内，利用光声成像技术确定光敏剂到达肿瘤部位后，确定最佳的治疗时间进行肿瘤细胞的杀伤。
本发明缺氧氧化铈CeO2-x@HA作为光敏剂，易于确定注射光敏剂后治疗肿瘤细胞的最佳时间，对于生物体具有良好的生物相容性，且操作简单，成像速度快，成像效果好，而且对于肿瘤具有优异的杀伤效果。
附图说明
图1为实施例中HA、CeO2-x、CeO2-x@HA的红外谱图。
图2为实施例中CeO2-x、CeO2-x@HA的紫外吸收谱图。
图3为实施例中用CeO2-x@HA孵育4T1、L929、HeLa细胞的暗毒性试验。
图4为实施例中不同浓度的CeO2-x@HA的光声成像数据图。
具体实施方式
下面结合附图和实施例对本发明内容作进一步的说明，但不是对本发明 的限定。
实施例
制备缺氧氧化铈：
按质量比为1:0.8取氧化铈和硼氢化钠，将二者混合，在氩气保护下经过600℃高温管式炉反应2小时，得到黑色缺氧氧化铈；
将得到的黑色缺氧氧化铈加入研钵，加入二次水进行碾磨，吸取上层液体进行离心洗涤，采用水和乙醇交叉洗涤2-3次，将洗净的氧化铈溶于水，配置成60 mg/mL的溶液加入寡肽酶切透明质酸1g，在常温下搅拌2h，之后在90℃进行水热反应8h得到CeO2-x@HA。
通过红外，紫外以及光声成像等手段对CeO2-x@HA进行鉴定。
体外实验：通过体外细胞的MTT实验表明得到的CeO2-x@HA具有良好的生物相容性。用不同浓度的CeO2-x@HA（0、50、100、150、200、250、300 μg/mL）孵育4T1细胞、HeLa细胞以及L929细胞，孵育12 h后，加入MTT再孵育4 h之后弃去培养基加入100μL的DMSO，用酶标仪测定其吸光度。
实验数据如图1-4所示，通过图1可以看出采用本发明方法成功制备出了具有光声成像性能的肿瘤治疗光敏剂CeO2-x@HA。
通过图2可以看出采用本发明方法制备的CeO2-x@HA在近红外二区具有良好的光吸收性能，特征吸收在980 nm处，具有优异的光穿透深度。
图3表明制备的CeO2-x@HA具有良好的生物相容性，不同细胞4T1、L929、HeLa在孵育24 h后细胞存活率仍能达到80 %以上。
图4表明制备的CeO2-x@HA具有良好的光声成像性能，随浓度的升高信号强度及成像效果随之加强。
Claims (2)
1.一种具有光声成像性能的缺氧氧化铈的制备方法，其特征在于，所述制备方法为：
以氧化铈为原料，加入硼氢化钠，在氩气保护下经过600℃高温管式炉反应2小时，得到黑色缺氧氧化铈；
将得到的黑色缺氧氧化铈加入研钵，加入二次水进行碾磨，吸取上层液体进行离心洗涤，采用水和乙醇交叉洗涤2-3次，将洗净的氧化铈溶于水，配置成60 mg/mL的溶液加入寡肽酶切透明质酸1g，在常温下搅拌2h，之后在90℃进行水热反应8h得到CeO2-x@HA；
通过红外，紫外以及光声成像手段对CeO2-x@HA进行鉴定，并通过体外细胞的MTT实验表明得到的CeO2-x@HA具有良好的光热效果和光声成像性能。
2.根据权利要求1所述的具有光声成像性能的缺氧氧化铈的制备方法，其特征在于：所述氧化铈与硼氢化钠的质量比为1:0.8。
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| CN110156072B (zh) * | 2019-06-29 | 2021-05-25 | 西南大学 | 连接Ce6缺氧型黑色二氧化钛纳米颗粒的制备方法 |
| CN110538332A (zh) * | 2019-10-14 | 2019-12-06 | 祝守慧 | 一种具有肿瘤靶向和放疗增敏特性的复合纳米颗粒及其制备与应用 |
| CN110917350B (zh) * | 2019-12-27 | 2021-08-10 | 广西师范大学 | 一种黑色二氧化锡纳米光热材料的制备及其应用 |
| CN111773243B (zh) * | 2020-07-17 | 2022-09-23 | 南京大学 | 炎症性肠病的药物及其制备方法和用途 |
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