CN114042168A - 一种双金属硫化物纳米探针的制备及应用 - Google Patents
一种双金属硫化物纳米探针的制备及应用 Download PDFInfo
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Abstract
本发明公开一种双金属硫化物纳米探针的制备及应用,属于纳米生物材料技术领域,更具体地,涉及一种金属有机框架材料衍生的双金属硫化物纳米探针的制备及应用。本发明将一锅法制备得到的钴的金属有机框架材料ZIF‑67进行硫化处理和离子交换,得到双金属硫化物FexCoSy纳米材料。以该材料进行癌症治疗时,能够同时通过光热治疗、化学动力学以及铁死亡的途径来治愈癌症;同时,FexCoSy还具有光声成像和核磁共振成像的能力,能够实现成像介导下的精准治疗;再进一步修饰增加肿瘤靶向能力的聚合物DSPE‑PEG‑FA后,使该纳米材料能大量靶向到肿瘤部位,实现成像介导下的高靶向性癌症联合治疗,从而有效的杀死肿瘤细胞。
Description
技术领域
本发明属于纳米生物材料技术领域,更具体地,涉及一种双金属硫化物纳米探针的制备及应用。
背景技术
乳腺癌是女性最常见的的恶性肿瘤之一,其5年的存活率仅为20%。但是,目前乳腺癌的化疗和放疗效果较差且副作用大。因此,开发新型乳腺癌治疗诊断技术意义重大。
光热治疗时利用光热效应产生高温来杀伤癌细胞的一种癌症治疗方法,几乎对所有类型的肿瘤都有治疗效果。相对于光动力学治疗,光热治疗无需氧气参与,不受肿瘤乏氧状态的制约,在乳腺癌及其它癌症的治疗中展现出独特的优势。迄今,已有多种光热转换材料,包括金纳米棒、碳纳米管、有机分子、聚合物等,用于乳腺癌治疗。但是,乳腺癌异质性高,单模式的光热治疗可能治疗不彻底,引起肿瘤复发。因此,积极开发联合多种治疗模式来提升乳腺癌的治疗效果迫在眉睫。
发明内容
针对现有技术的以上缺陷或改进需求,本发明的目的是提供了一种双金属硫化物纳米探针的制备及应用,其通过将一锅法制备得到的钴的金属有机框架的纳米材料ZIF-67进行硫化处理和离子交换,得到钴和铁的双金属硫化物纳米材料,并将其用于制备多模式治疗的乳腺癌肿瘤的探针,由此解决现有技术的乳腺癌治疗不彻底,容易引起复发的技术问题。
本发明的目的是这样实现的,一种双金属硫化物纳米材料的制备方法,其特征在于,包括如下步骤:
(1)通过一锅法合成钴的金属有机框架纳米材料ZIF-67;
(2)对步骤(1)得到的钴的金属有机框架纳米材料ZIF-67进行硫代,得到硫化钴CoSy纳米材料;
(3)对步骤(2)得到的CoSy纳米材料进行铁离子交换,得到FexCoSy纳米材料。
上述步骤(1)具体制备方法为:以六水合硝酸钴为金属离子,以2-甲基咪唑为有机框架,通过一锅法合成金属有机框架的纳米材料ZIF-67。
上述步骤(2)中硫代处理的试剂为硫代乙酰胺,硫代反应的温度为120-160℃,硫代煅烧的时间为1-4h。
上述步骤(3)中离子交换时所用试剂为五水合二氯化铁,离子交换反应的溶剂为乙醇,离子交换反应的温度为80-160 ℃,离子交换的煅烧时间为0.5-8h。
本发明上述的制备方法得到的双金属硫化物纳米材料。
本发明所述的双金属硫化物纳米材料的应用,其特征在于,在制备治疗肿瘤的纳米探针中的应用。
上述治疗肿瘤的纳米探针为通过光热、铁死亡、化学动力学的方式联合治疗肿瘤的纳米探针。
所述的应用,其特征在于,应用前,将所述双金属硫化物纳米材料进行聚乙二醇修饰。
具体地说,为实现上述目的,按照本发明的一个方面,提供了一种双金属硫化物纳米材料的制备方法,包括如下步骤:
(1)通过一锅法合成钴的金属有机框架的纳米材料ZIF-67;
(2)对步骤(1)得到的钴的金属有机框架的纳米材料ZIF-67进行硫化处理,得到CoSy纳米材料。
优选地,步骤(1)具体为:以六水合硝酸钴的钴离子为金属离子,以2-甲基咪唑为有机框架,通过一锅法合成金属有机框架的纳米材料ZIF-67。
优选地,所述六水合硝酸钴与2-甲基咪唑的摩尔比为1:80-120。
优选地,步骤(2)具体为:将ZIF-67纳米颗粒与硫代乙酰胺分散在无水乙醇中,转至水热反应釜中,高温煅烧得到CoSy纳米颗粒。所述煅烧在100-140 ℃范围内进行,煅烧时间3-5h。
按照本发明的另一个方面,提供了一种所述的制备方法得到的双金属硫化物纳米材料。
按照本发明的另一个方面,提供了一种所述的双金属硫化物纳米材料的应用,用于制备治疗肿瘤的纳米探针。
优选地,所述治疗肿瘤的纳米探针为光热、铁死亡和化学动力学三种方式治疗肿瘤的纳米探针,治疗的肿瘤为乳腺癌肿瘤。
优选地,应用前,将所述双金属硫化物纳米材料进行聚乙二醇修饰。
总体而言,通过本发明所构思的以上技术方案与现有技术相比,能够取得下列有益效果:
(1)本发明将一锅法制备得到的Co的金属有机框架的纳米材料ZIF-67进行硫代处理,得到CoSy纳米材料。该纳米材料呈中空圆球形貌,直径约为150-250纳米,具有多孔性结构。
(2)本发明通过一锅法合成钴的有机金属框架纳米材料,通过硫代处理和高温煅烧得到钴的硫化物CoSy。通过离子交换得到Fe含量不同的FexCoSy, 在此基础上修饰水溶性的聚乙二醇,赋予材料更好的水溶性和生物相容性。
(3)本发明优选地在以ZIF-67作为前体,ZIF-67本身作为MOF,很好的利用了其本身具有的永久多孔性结构。
(4)本发明所涉及的FexCoSy本身具有过氧化物酶催化活性,以此FexCoSy为载体进行癌症治疗时能够将肿瘤微环境的过氧化氢催化为氧气,提高肿瘤细胞中的氧气含量,进而增加化学动力学和光热治疗的效率;再经过修饰上靶向叶酸的聚乙二醇DSPE-PEG-FA后,赋予该纳米材料更好的靶向到肿瘤的效果,从而实现有效的杀死肿瘤细胞。
附图说明
图1 是合成的ZIF-67,CoSy,和FexCoSy的透射电镜图,标尺分别是200 nm,200 nm和100 nm。
图2是空白组,CoSy,和FexCoSy与TMB反应后,催化oxTMB产生的量图。
具体实施方式
为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。此外,下面所描述的本发明各个实施方式中所涉及到的技术特征只要彼此之间未构成冲突就可以相互组合。
本发明提供了一种MOF衍生的双金属硫化物纳米材料的制备方法,包括如下步骤:
(1)通过一锅法合成钴的金属有机框架的纳米材料ZIF-67;
(2)对步骤(1)得到的ZIF-67进行硫代处理和高温煅烧,得到硫化钴CoSy。
(3)对步骤(2)得到的CoSy进行离子交换,将CoSy的乙醇溶液与一定量的FeCl2溶液混合后,高温煅烧得到双金属硫化物FexCoSy。
一些实施例中,步骤(1)具体为:以六水合硝酸钴(CO(NO3)2·6H2O)的钴离子为金属盐,以2-甲基咪唑(2-Methylimidazole, 2-mIm)为有机框架,通过一锅法合成金属有机框架的纳米材料ZIF-67。
本发明所述一锅法即为,将六水合硝酸钴的水溶液与有机框架的水溶液混合搅拌,制备得到ZIF-67。一些实施例中,六水合硝酸钴与有机框架的用量范围可以根据需要进行调整,以得到具有合适的形貌的ZIF-67。所述六水合硝酸钴与2-甲基咪唑的摩尔比优选为1:12-85。在一个反应体系中,六水合硝酸钴的用量为物质的量1-3 mmol,有机框架2-甲基咪唑的用量为质量3-7 g。
一些实施例中,步骤(2)具体为:所述煅烧在100-140 ℃范围内进行,煅烧时间为3-5h。本发明煅烧在空气气氛下进行。
一些实施例中,步骤(3)具体为:所述煅烧在140-180 ℃范围内进行,煅烧时间为3-5h。本发明煅烧在空气气氛下进行。
本发明还提供了所述的制备方法得到的双金属硫化物纳米材料。
本发明制备方法步骤(1)制备得到的钴的金属有机框架的纳米材料ZIF-67为中空的圆球状结构,直径范围为150-250 nm;离子交换和高温煅烧后得到的硫化钴保持了中空圆球的结构,但中空的程度大大增加。
本发明制得的硫化物纳米探针具有过氧化物酶的催化活性,能够将过氧化氢催化成氧气,优选地,将该探针应用到细胞治疗或活体治疗中,其能够催化癌细胞中富集的过氧化氢转化为氧气,同时能够增强光动力治疗的效率。
本发明提供的双金属硫化钴纳米探针,其前体为金属有机框架ZIF-67,通过硫代处理和高温煅烧得到CoSy,再通过离子交换得到FexCoSy。相较于ZIF-67具有更大程度的中空结构,相较于CoSy具有更好的催化性能和光热转换性能;同时,引入Fe元素后,形成的双金属硫化物可进行化学动力学,从而更有效的杀伤癌细胞和肿瘤。
本发明所述的双金属硫化物纳米材料的应用,可用于制备治疗肿瘤的纳米探针。
一些实施例中,应用前,将所述双金属硫化物纳米材料进行含有叶酸的聚乙二醇的修饰。具体地,通过将FexCoSy与DSPE-PEG-FA搅拌后,室温下过夜反应,能够获得靶向能力增强的纳米探针FexCoSy-PEG-FA。
本发明进一步提供了上述探针FexCoSy-PEG-FA的制备方法,包括以下步骤:
(1)以六水合硝酸钴的钴离子为金属离子,以2-甲基咪唑为有机框架,通过一锅法合成ZIF-67。
(2)将(1)中的ZIF-67通过硫代处理和高温煅烧,得到CoSy。
(3)将(2)中的CoSy与FeCl2在高温下反应后,得到FexCoSy。
(4)在(3)的基础上修饰能增加靶向能力和探针水溶性的DSPE-PEG-FA。
具体地,步骤(1)中,通过如下方法制备得到锰的金属有机框架:
1)分别配置六水合硝酸锌和2-甲基咪唑的溶液备用:具体地,六水合硝酸锌的溶液为1-3 mmol溶于3 mL水中,和2-甲基咪唑的溶液为3-7g溶于20mL水中,,备用。
2)在剧烈搅拌装有步骤1)配制好的咪唑溶液中,逐滴加入六水合硝酸锌溶液,室温持续搅拌5-7 h,颜色由无色最终变成深紫色,离心洗去未反应的钴离子和咪唑,得到深紫色的沉淀物即为CoSy。
3)将一定量FeCl2与CoSy乙醇溶液混合,高温煅烧后,颜色由深紫色变成黑色,离心去除未反应的铁离子,得到黑色的沉淀即为双金属硫化物FexCoSy。
4)将修饰有叶酸的DSPE-PEG-FA(分子质量5000 Da)与FexCoSy室温混合过夜,得到探针FexCoSy-PEG-FA。
在步骤(2)中,将硫代乙酰胺溶液加到ZIF-67溶液中,加入马弗炉中进行高温煅烧,煅烧温度为100-140℃,煅烧时间为3-5 h,得到钴的硫化物CoSy。
在步骤(3)中,将FeCl2加到CoSy中后进行高温煅烧,煅烧温度为140-180℃,煅烧时间为3-5 h,得到双金属硫化物FexCoSy。
本发明还提出了上述材料在异种移植的小鼠肿瘤模型中的应用。
本发明用下列实施例来进一步说明本发明,但本发明的保护范围并不限于下列实施例。
实施例1
一种双金属硫化物FexCoSy-PEG-FA纳米探针的制备方法,包括以下步骤:
(1)以六水合硝酸钴的钴离子为金属离子,以2-甲基咪唑为有机框架,通过一锅法合成ZIF-67。
(2)将(1)中的ZIF-67通过硫代处理和高温煅烧,得到CoSy。
(3)将(2)中的CoSy与FeCl2反应后,通过离子交换得到FexCoSy。
(4)在(3)的基础上修饰聚乙二醇DSPE-PEG-FA。
具体地,步骤(1)中,通过如下方法制备得到钴的金属有机框架:
1)分别配置四水合氯化锰和2-甲基咪唑的溶液备用:将0.2 g六水合硝酸钴溶于3mL超纯水中并超声分散均匀得到六水合硝酸钴的水溶液;将5.5 g 2-甲基咪唑溶于20 mL水中并超声分散均匀得到咪唑的水溶液,备用。
2)在剧烈搅拌装有20 mL步骤1)制得的咪唑溶液中,逐滴加入3 mL六水合硝酸钴溶液,室温持续搅拌6 h,颜色由无色最终变成深紫色,离心洗去未反应的钴离子和咪唑,得到深紫色的沉淀物即为钴的有机金属框架。
在步骤(2)中,将上述步骤(1)得到的ZIF-67(钴的有机金属框架)称取80 mg, 加入0.12 g硫代乙酰胺后,在马弗炉中进行高温煅烧,煅烧温度为120℃,煅烧时间为4 h,获得CoSy。
在步骤(3)中,将步骤(2)制备的CoSy称取10 mg溶于20 mL无水乙醇溶液中, 再加入100 μL浓度为5.05 mmol/L的FeCl2溶液,(所述的浓度为5.05 mmol/L的FeCl2溶液配置方法为:称取9 mg FeCl2溶于3 mL无水乙醇中配置成浓度为5.05 mmol/L的FeCl2溶液),在马弗炉中进行高温煅烧,煅烧温度为160℃,煅烧时间为4 h,获得FexCoSy。
在步骤(4)中,将步骤(3)制备的FexCoSy与适量的DSPE-PEG-FA,搅拌过夜后,6000rpm离心10 min,用超纯水洗三次除去未反应的PEG,得到FexCoSy-PEG-FA。
实施例2
本实施例提供了一种双金属硫化物纳米探针的合成方法,该材料呈中空的圆球状,其直径范围为150 nm-250 nm;
该材料由如下制备方法制备得到:
(1)ZIF-67的制备
在剧烈搅拌的20 mL含有5.5 g 2-mIm的水反应体系中,逐滴加入3 mL 溶解有0.2g的六水合硝酸钴溶液,室温持续搅拌6 h,颜色由无色变成深紫色,通过6000 rpm,10 min离心洗去未反应的金属离子和咪唑,得到深紫色的沉淀物即为ZIF-67。
如图1所示,为步骤(1)所得到的ZIF-67的透射电镜形貌图,得到的ZIF-67直径的范围为15-250 nm,且具有较好的分散性。
(2)CoSy的制备
将步骤(1)所得到的ZIF-67称取80 mg后,再称取0.2 g硫代乙酰胺,两者溶于40mL无水乙醇后,置于马弗炉中进行高温煅烧120℃,4 h,得到钴的硫化物CoSy。
如图1所示,为得到的CoSy的透射电镜形貌图,形貌与ZIF-67相比并无较大差异,但是具有更明显的中空结构。
(3)FexCoSy的制备
将步骤(2)中的一定量FeCl2与10 mg步骤(1)所得到的 CoSy的乙醇溶液混合,160℃反应4 h,得到双金属硫化物FexCoSy。
如图1所示,为得到的FexCoSy的透射电镜形貌图,形貌与CoSy相比并无较大差异。
(4)FexCoSy-PEG-FA的制备
将2 mg修饰有叶酸的DSPE-PEG-FA(分子质量5000 Da)与10 mg 步骤(3)所得到的FexCoSy纳米材料室温混合过夜。
实施例3
有机金属框架用于乳腺癌的材料表征,其步骤是:
表征制备的有机金属框架的催化性能时,将合成的CoSy, FexCoSy纳米材料溶于水,与TMB反应,在5 min内通过测定650 nm的吸收值来表示反应体系中oxTMB的量。
图2为不同纳米颗粒的催化能力,结果表明CoSy不具有催化能力,当离子交换后,FexCoSy能够很好的持续催化反应体系中的TMB,表明其具有很好地过氧化物酶活性。
本领域的技术人员容易理解,以上所述仅为本发明的较佳实施例而已,并不用以限制本发明,凡在本发明的精神和原则之内所作的任何修改、等同替换和改进等,均应包含在本发明的保护范围之内。
Claims (8)
1.一种双金属硫化物纳米材料的制备方法,其特征在于,包括如下步骤:
(1)通过一锅法合成钴的金属有机框架纳米材料ZIF-67;
(2)对步骤(1)得到的钴的金属有机框架纳米材料ZIF-67进行硫代,得到硫化钴CoSy纳米材料;
(3)对步骤(2)得到的CoSy纳米材料进行铁离子交换,得到FexCoSy纳米材料。
2.如权利要求1所述的制备方法,其特征在于,步骤(1)具体制备方法为:以六水合硝酸钴为金属离子,以2-甲基咪唑为有机框架,通过一锅法合成金属有机框架的纳米材料ZIF-67。
3.如权利要求1所述的制备方法,其特征在于,步骤(2)中硫代处理的试剂为硫代乙酰胺,硫代反应的温度为120-160℃,硫代煅烧的时间为1-4h。
4.如权利要求1所述的制备方法,其特征在于,步骤(3)中离子交换时所用试剂为五水合二氯化铁,离子交换反应的溶剂为乙醇,离子交换反应的温度为80-160 ℃,离子交换的煅烧时间为0.5-8h。
5.如权利要求1至4任一项所述的制备方法得到的双金属硫化物纳米材料。
6.如权利要求5所述的双金属硫化物纳米材料的应用,其特征在于,在制备治疗肿瘤的纳米探针中的应用。
7.如权利要求6所述的应用,其特征在于,所述治疗肿瘤的纳米探针为通过光热、铁死亡、化学动力学的方式联合治疗肿瘤的纳米探针。
8.如权利要求6所述的应用,其特征在于,应用前,将所述双金属硫化物纳米材料进行聚乙二醇修饰。
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CN115054691A (zh) * | 2022-07-15 | 2022-09-16 | 中山大学附属第七医院(深圳) | 一种三元硫族金属纳米粒子及其制备方法和应用 |
CN117138055A (zh) * | 2023-06-02 | 2023-12-01 | 中山大学附属第一医院 | 一种双载体的阿霉素载药纳米材料及其制备方法 |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109835937A (zh) * | 2017-11-29 | 2019-06-04 | 中国科学院大连化学物理研究所 | 金属有机骨架化合物衍生的金属硫化物纳米片及其制备 |
US20190247502A1 (en) * | 2018-02-13 | 2019-08-15 | American University Of Sharjah | Ultrasound triggered release from metal organic framework nanocarriers |
CN110876804A (zh) * | 2019-11-04 | 2020-03-13 | 华中科技大学 | 一种多孔性四氧化三锰纳米探针的制备及应用 |
CN110961159A (zh) * | 2019-12-31 | 2020-04-07 | 五邑大学 | 一种负载型Fe-Co/ZIF-67双金属催化剂及其制备方法与应用 |
-
2021
- 2021-11-09 CN CN202111320777.2A patent/CN114042168B/zh active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109835937A (zh) * | 2017-11-29 | 2019-06-04 | 中国科学院大连化学物理研究所 | 金属有机骨架化合物衍生的金属硫化物纳米片及其制备 |
US20190247502A1 (en) * | 2018-02-13 | 2019-08-15 | American University Of Sharjah | Ultrasound triggered release from metal organic framework nanocarriers |
CN110876804A (zh) * | 2019-11-04 | 2020-03-13 | 华中科技大学 | 一种多孔性四氧化三锰纳米探针的制备及应用 |
CN110961159A (zh) * | 2019-12-31 | 2020-04-07 | 五邑大学 | 一种负载型Fe-Co/ZIF-67双金属催化剂及其制备方法与应用 |
Non-Patent Citations (3)
Title |
---|
施利毅主编: "《MOF材料的动态框架、模板效应、孔径调节及应用》", vol. 1, 上海科学普及出版社, pages: 129 - 130 * |
李思奇: "基于铁、钴金属-有机框架材料的新型纳米酶设计和生化分析应用研究", 《中国博士学位论文全文数据库工程科技Ⅰ辑》, no. 1, pages 014 - 200 * |
李思奇: "基于铁、钴金属-有机框架材料的新型纳米酶设计和生化分析应用研究", no. 1, pages 014 - 200 * |
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CN117138055A (zh) * | 2023-06-02 | 2023-12-01 | 中山大学附属第一医院 | 一种双载体的阿霉素载药纳米材料及其制备方法 |
CN117138055B (zh) * | 2023-06-02 | 2024-04-16 | 中山大学附属第一医院 | 一种双载体的阿霉素载药纳米材料及其制备方法 |
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