CN111498907A - 掺杂的Keggin型杂多酸的制备方法及其应用 - Google Patents
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Abstract
本发明提供了一种掺杂的Keggin型杂多酸的制备方法，其包括如下步骤：将钨酸钠加入钼酸铵水溶液中，混匀后，加入L‑抗坏血酸，反应后加入乙醇，离心分离出沉淀，用水和乙醇进行洗涤后，冷冻干燥，得到所述钨掺杂的Keggin型杂多酸。本发明的有益效果在于，本发明制备的W‑POM在正常组织的pH条件下(pH7.4)粒径范围在10～50nm，感染部位的pH条件下(pH 6.4)会发生自聚集后粒径范围在110～1100nm。
Description
技术领域
本发明涉及一种掺杂的Keggin型杂多酸的制备方法及其应用，属于杂多酸的制备和应用技术领域。
背景技术
抗生素的出现为细菌感染性疾病的治疗带来了曙光，然而数十年来的抗生素使用逐渐暴露出传统抗生素治疗的弊端：(1)生物利用率低；(2)长期大量使用导致细菌耐药性的产生；(3)对生物膜或细胞内细菌的杀伤效果较差。
光热疗法(PTT)是利用具有光热性能的材料，在光照条件下将光能转化为热能，产生局部高温从而实现对细菌物理杀伤的新型治疗模式。与抗生素治疗相比，光热疗法可广谱抗菌，穿透力更强，耐药性更低。化学动力疗法(CDT)是利用铁或其他金属离子将炎症部位过度表达的过氧化氢(H2O2)转化为羟基自由基(·OH)，进而对细胞造成不可逆损伤的治疗手段。若仅使用PTT会造成过高温而损伤正常组织，仅使用CDT易因环境介质的不充足而效率低下。结合两种或以上材料能实现PTT/CDT协同治疗，但是这类材料的合成方法往往较为繁琐复杂，成本较高，不适合量产。
发明内容
针对现有技术中的缺陷，本发明的目的是提供一种掺杂的Keggin型杂多酸的制备方法及其应用。
一种掺杂的Keggin(凯格恩)型杂多酸的制备方法，其包括如下步骤：
将金属盐加入钼酸铵水溶液中，混匀后，加入L-抗坏血酸，反应4-8小时后加入乙醇，离心分离出沉淀，用水和乙醇进行洗涤后，冷冻干燥，得到所述钨掺杂的Keggin型杂多酸。
作为优选方案，所述金属盐为钨酸钠或氯化铁。
作为优选方案，钨元素和钼元素的摩尔比为1:(1～3)。
作为优选方案，所述L-抗坏血酸的质量与钼酸铵质量比为(1～3):1。
作为进一步优选方案，所述L-抗坏血酸的质量与钼酸铵质量比为2:1，质量比1:1会导致杂多酸还原不充分，3:1会造成L-抗坏血酸的浪费。
一种由前述的制备方法得到的掺杂的Keggin型杂多酸。
一种如前述的掺杂的Keggin型杂多酸在光热疗法和化学动力疗法协同抗菌药物中的用途。
与现有技术相比，本发明具有如下的有益效果：
1、目前大多数响应性纳米药物需要通过复杂的多层修饰来实现靶向传递。本发明的钨钼酸纳米颗粒采用一锅法进行合成，操作简便，有利于进一步量产，并且能够通过自聚集实现药物从血液至感染部位的靶向聚集及滞留，以提高药物的利用率。制备的W-POM在正常组织的pH条件下(pH 7.4)粒径范围在10～50nm，感染部位的pH条件下(pH 6.4)会发生自聚集后粒径范围在110～1100nm。
2、本发明所得到的W-POM在正常组织的pH条件下(pH 7.4)对近红外区辐射的吸收较弱，然而在感染部位的pH条件下(pH 6.4)对近红外区辐射的吸收较强，这种光热转换能力的调节性，可以降低对正常组织的损伤。在808nm红外光激发下，250μg/ml pH为6.4的W-POM溶液在10分钟内可升温24℃左右。目前已报道一种具相同功能的金属卟啉锌，其光热转换效率为30.0％，而本发明出的钨钼酸光热转换效率在40％以上。在杂多酸结构中，最低未占据轨道(LUMO)主要定位在Mo原子上，而最高占据轨道(HOMO)主要定位在桥架氧(Oc和Oe)上，其近红外光热转换能力来自于POM中Mo(V)和Mo(VI)之间通过桥接氧键的电荷转移，在酸性条件下，通过钨钼酸桥架氧的质子化进一步扩大HOMO轨道与LUMO轨道间间隙，所以近红外吸收峰更接近于组织穿透深度较强的1060nm。
3、本发明所得的W-POM在进入体内后，过氧化氢被Mo还原，产生具有破坏脂类、蛋白质、DNA等生物分子的能力的羟基自由基，以促进化学动力抗菌治疗。Mo(VI)又会被体内原有的谷胱甘肽(GSH)再次还原成Mo(V)，提高光热治疗效果。还原型GSH被消耗，破坏了细胞内氧化还原平衡，提高了CDT效果。与需要多种材料结合才能实现多模态治疗的药物不同，本专利发明的W-POM能够利用感染部位原有的物质进行光热与化学动力协同治疗，显著提高抗菌效果。此外，W-POM在正常组织弱碱性环境中的近红外吸收较弱，减轻PTT对正常组织的损伤。弱碱性还会抑制芬顿反应的催化速率，减轻CDT对正常组织的损伤。
4、本发明所得的两种POM能在炎症处由于酸聚集延长滞留时间，均具有NIR-II光热治疗和化学动力学治疗效果，且由于Mo(VI)与Mo(V)的氧化还原循环破坏细胞内氧化还原平衡，提高了CDT效果。本发明所得的Fe-POM在Fe2+作用下表现出更强的CDT效果。本发明所得的W-POM由于W的掺杂加剧了局部表面等离子体激元共振，增强了PTT效果。
附图说明
通过阅读参照以下附图对非限制性实施例所作的详细描述，本发明的其它特征、目的和优点将会变得更明显：
图1为本发明中实施例1制备的钨钼酸在不同pH值条件下的TEM图像(a图pH为7.4，b图pH为6.4)；弱碱性下极小的颗粒有助于体内的快速代谢，弱酸性下自聚集的大尺寸有利于炎症处的长时间积累。
图2为本发明中实施例1制备的钨钼酸在不同pH值条件下的DLS结果(a图pH为7.4，b图pH为6.4)；粒径分析进一步证实了上述结果；
图3为本发明中实施例1制备的钨钼酸在不同浓度或pH值下的紫外-可见光谱；弱碱性下吸收很弱，降低了W-POM的光热效果，弱酸性下的第二近红外吸收使得W-POM有二区光热的能力；
图4为本发明中实施例1制备的钨钼酸的XPS谱；证实了W-POM中钨元素和钼元素的存在；
图5为本发明中实施例1制备的钨钼酸在不同pH和浓度下在1060nm激光照射(1Wcm-2)下的光热性能测试结果；弱碱性下光热效果明显比弱酸性下差，保护了炎症周围的正常组织；
图6为本发明中实施例1制备的钨钼酸在不同pH和温度条件下对芬顿反应效果(以亚甲基蓝为探针)；表明弱酸性和高温对芬顿反应有明显的促进作用；
图7为本发明中实施例1制备的钨钼酸在不同浓度溶液中的GSH的消耗量(以DTNB为探针)；表明W-POM可以有效消耗GSH，提高CDT效率；
图8为本发明中实施例1制备的钨钼酸在不同pH值条件下的抑菌效果(a图pH为6.4，b图pH为7.4)；弱酸性下抑菌效果显著优于弱碱性下，表明其有效的抑菌能力和对周围正常组织的保护作用；
图9为本发明中实施例1制备的钨钼酸在不同pH值条件下的处理金黄色葡萄球菌后的SEM照片(a图pH为7.4，b图pH为6.4)。弱碱性下细菌基本无损伤，弱酸性下细菌出现褶皱、破裂和内容物流出。这表明W-POM在弱酸性下对细菌有良好的杀伤能力。
具体实施方式
下面结合具体实施例对本发明进行详细说明。以下实施例将有助于本领域的技术人员进一步理解本发明，但不以任何形式限制本发明。应当指出的是，对本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进。这些都属于本发明的保护范围。
实施例1
本实施例提供了一种钨掺杂的Keggin型杂多酸的制备方法，具体包括如下步骤：
首先将0.4414g(NH4)6Mo7O24·4H2O溶解在10mL的超纯水中，在25℃下连续搅拌，然后快速加入5mL的0.0074g Na2WO4溶液，最后，为了得到还原态的W-POM，在搅拌下向体系中滴加2mL的0.8828g·L-1L-抗坏血酸溶液。在25℃下进一步搅拌2h后，加入80mL乙醇沉淀，离心收集，用水和乙醇洗涤3次，最后在冻干机中干燥得到。图1a和图1b分别是本实施例合成的杂多酸在pH＝7.4和pH＝6.4下的TEM照片，图2a和图2b分别是本实施例合成的杂多酸在pH＝7.4和pH＝6.4下的粒径，表明了杂多酸在酸性条件下会有良好的聚集。图3是本实施例合成的杂多酸在不同浓度或pH值下的紫外-可见光谱；弱碱性下吸收很弱，降低了W-POM的光热效果，弱酸性下的第二近红外吸收使得W-POM有二区光热的能力。图4是本实施例合成的杂多酸的XPS谱，证实了W-POM中钨元素和钼元素的存在。
将本实施例得到的杂多酸粉末进行性能测试，具体方法为：
用1060nm激光辐照1mL W-POM水溶液(pH 6.4，100、200、250μg mL-1和pH 7.4，250μg mL-1)。W-POM水溶液的温度通过近红外温度照相机记录。图5是杂多酸在不同pH和浓度下在1060nm激光照射(1W·cm-2)下的光热性能测试结果；弱碱性下光热效果明显比弱酸性下差，保护了炎症周围的正常组织。
将W-POM添加到含有10μg mL-1MB，10mM H2O2的溶液中，并在四种不同条件下孵育(pH 7.4/37℃；pH 7.4/50℃；pH 6.4/37℃；pH 6.4/50℃)20分钟。通过·OH诱导的亚甲基蓝(MB)降解分析·OH的生成。图6是杂多酸在不同pH和温度条件下对芬顿反应效果(以亚甲基蓝为探针)；表明弱酸性和高温对芬顿反应有明显的促进作用，将本实施例合成的钨钼酸在不同浓度溶液中测试GSH的消耗量(以DTNB为探针)，结果如图7所示，表明W-POM可以有效消耗GSH，提高CDT效率。
将本实施例得到的杂多酸粉末应用于体内外抗菌，具体方法为：
a、以革兰氏阳性金黄色葡萄球菌(S.aureus)为模型菌，研究W-POM的抑菌性能。用不同pH值的PBS缓冲溶液将细菌稀释至106个CFU mL-1。将W-POM也溶于pH6.4的PBS缓冲溶液中，用浓度为500μg·mL-1的W-POM溶液处理细菌稀释液，并用1060nm激光(1W·cm-2)照射5min。在37℃，180rpm下培养4小时后测定细菌稀释液在600nm处的吸光度。将100μL的上述菌悬液涂抹在固体培养基上，37℃孵育18小时，计算菌落数、细菌存活率并观察细菌形态。图8a和图8b分别为本实施例合成的钨钼酸在pH＝6.4和pH＝7.4条件下的抑菌效果。弱酸性下抑菌效果显著优于弱碱性下，表明其有效的抑菌能力和对周围正常组织的保护作用。图9a和图9b分别为本实施例制备的杂多酸在pH＝6.4和pH＝7.4条件下处理后金黄色葡萄球菌后的SEM照片，弱酸性下细菌出现褶皱、破裂和内容物流出。这表明W-POM在弱酸性下对细菌有良好的杀伤能力。
b、在雌性Balb/c小鼠(4～5周，20～22g)上皮下接种金黄色葡萄球菌，建立皮下脓肿模型。尾静脉注射25μL浓度为500μg·mL-1的W-POM溶液射2小时后，用1060nm激光(1W·cm-2)照射脓肿5min。监测脓肿部位的升温情况。每天记录体重并拍摄脓肿，治疗10天后，创面基本愈合。3天后，每组各处死1只小鼠，取皮肤组织。10天后处死小鼠，取出主要脏器(心、肝、脾、肺、肾)，H&E染色处理后进行组织学分析。治疗后未见明显的器官损伤或炎症损伤，说明W-POM对正常组织的毒性较低。验证了W-POM的CDT/PTT协同快速有效灭菌能力。
实施例2
本实施例提供了一种铁掺杂的Keggin型杂多酸的制备方法，具体包括如下步骤：
首先将0.4414g(NH4)6Mo7O24·4H2O溶解在10mL的超纯水中，在25℃下连续搅拌。然后快速加入5mL的0.1756g FeCl3水溶液。最后，为了得到还原态的Fe-POM，在搅拌下向体系中滴加2mL的含0.8828g抗坏血酸的水溶液。在25℃下进一步搅拌2h后，加入80mL乙醇沉淀，离心收集，用水和乙醇洗涤3次，最后在冻干机中干燥得到杂多酸粉末。
将本实施例得到的杂多酸粉末应用于体内外抗菌，具体方法为：
a、以革兰氏阳性金黄色葡萄球菌(S.aureus)为模型菌，研究Fe-POM的抑菌性能。用不同pH值的PBS缓冲溶液将细菌稀释至106个CFU mL-1。将W-POM也溶于pH6.4的PBS缓冲溶液中，用浓度为500μg·mL-1的Fe-POM溶液处理细菌稀释液，并用1060nm激光(1W·cm-2)照射5min。在37℃，180rpm下培养4小时后测定细菌稀释液在600nm处的吸光度。将100μL的上述菌悬液涂抹在固体培养基上，37℃孵育18小时，计算菌落数、细菌存活率并观察细菌形态。
b、在雌性Balb/c小鼠(4～5周，20～22g)上皮下接种金黄色葡萄球菌，建立皮下脓肿模型。尾静脉注射25μL浓度为500μg·mL-1的Fe-POM溶液射2小时后，用1060nm激光(1W·cm-2)照射脓肿5min。监测脓肿部位的升温情况。每天记录体重并拍摄脓肿。3天后，每组各处死1只小鼠，取皮肤组织。10天后处死小鼠，取出主要脏器(心、肝、脾、肺、肾)，H&E染色处理后进行组织学分析。
本发明使用金属掺杂的Keggin型杂多酸作为抗菌剂进行抗菌治疗，该类型杂多酸抗菌剂不仅合成方法简单快捷，还具有在不同pH条件下的自我调节能力，表现出不同的生物毒性：
本发明制备的杂多酸在响应感染部位的偏酸性环境(pH 6.4)后能发生自聚集，表现出较强的光热效果，并利用感染部位原有的过氧化氢进行光热与化学动力协同治疗，毒性强，抗菌效果好。然而，该类型杂多酸在正常组织弱碱性环境中(pH 7.4)对近红外辐射的吸收较弱，抑制芬顿反应的催化速率也会收到抑制，毒性较弱，能减轻光热疗法与化学动力疗法对正常组织的损伤。
以上对本发明的具体实施例进行了描述。需要理解的是，本发明并不局限于上述特定实施方式，本领域技术人员可以在权利要求的范围内做出各种变形或修改，这并不影响本发明的实质内容。
Claims (7)
1.一种掺杂的Keggin型杂多酸的制备方法，其特征在于，包括如下步骤：
将金属盐加入钼酸铵水溶液中，混匀后，加入L-抗坏血酸，反应4-8小时后加入乙醇，离心分离出沉淀，用水和乙醇进行洗涤后，冷冻干燥，得到所述钨掺杂的Keggin型杂多酸。
2.如权利要求1所述的掺杂的Keggin型杂多酸的制备方法，其特征在于，所述金属盐为钨酸钠或氯化铁。
3.如权利要求2所述的掺杂的Keggin型杂多酸的制备方法，其特征在于，钨元素和钼元素的摩尔比为1:(1～3)。
4.如权利要求1所述的掺杂的Keggin型杂多酸的制备方法，其特征在于，所述L-抗坏血酸的质量与钼酸铵质量比为(1～3):1。
5.如权利要求4所述的掺杂的Keggin型杂多酸的制备方法，其特征在于，所述L-抗坏血酸的质量与钼酸铵质量比为2:1。
6.一种由权利要求1所述的制备方法得到的掺杂的Keggin型杂多酸。
7.一种如权利要求6所述的掺杂的Keggin型杂多酸在光热疗法和化学动力疗法协同抗菌药物中的用途。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102230220A (zh) * | 2011-06-02 | 2011-11-02 | 东北师范大学 | 基于Keggin型硅钨酸盐的钼蓝微米管的制备及应用 |
| CN106513044A (zh) * | 2016-10-12 | 2017-03-22 | 上海应用技术大学 | (R)‑1‑(1‑苯乙基)硫脲单侧修饰的Fe‑Anderson型杂多酸催化剂、制备方法及其应用 |
| CN108785671A (zh) * | 2017-05-03 | 2018-11-13 | 首都师范大学 | 钼蓝杂多酸在作为光热转换材料中的应用 |
-
2020
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102230220A (zh) * | 2011-06-02 | 2011-11-02 | 东北师范大学 | 基于Keggin型硅钨酸盐的钼蓝微米管的制备及应用 |
| CN106513044A (zh) * | 2016-10-12 | 2017-03-22 | 上海应用技术大学 | (R)‑1‑(1‑苯乙基)硫脲单侧修饰的Fe‑Anderson型杂多酸催化剂、制备方法及其应用 |
| CN108785671A (zh) * | 2017-05-03 | 2018-11-13 | 首都师范大学 | 钼蓝杂多酸在作为光热转换材料中的应用 |
Non-Patent Citations (1)
| Title |
|---|
| YUNHAO SHI等: "Fe-Doped Polyoxometalate as Acid-Aggregated Nanoplatform for NIR-II Photothermal-Enhanced Chemodynamic Therapy", 《ADV. HEALTHCARE MATER》 * |
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