CN110101860A - 铋掺杂的金属硫化物纳米花及其制备方法 - Google Patents
铋掺杂的金属硫化物纳米花及其制备方法 Download PDFInfo
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- CN110101860A CN110101860A CN201910349442.XA CN201910349442A CN110101860A CN 110101860 A CN110101860 A CN 110101860A CN 201910349442 A CN201910349442 A CN 201910349442A CN 110101860 A CN110101860 A CN 110101860A
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- Prior art keywords
- solution
- flower
- metal sulfide
- nano metal
- bismuth
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Links
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- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 claims abstract description 15
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Abstract
本发明涉及一种铋掺杂的金属硫化物纳米花及其制备方法,制备方法为:将同时含有中间体粒子和四水硫代钼酸铵的溶液体系进行溶剂热反应制得铋掺杂的金属硫化物纳米花;中间体粒子是通过将A溶液和B溶液混合生成的,A溶液主要由BiCl3、MnCl2·4H2O和去离子水组成,B溶液主要由K4[Fe(CN)6]·3H2O、柠檬酸和去离子水组成;最终制得的铋掺杂的金属硫化物纳米花为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片。本发明的制备方法简单,制得的纳米花能实现单一结构容纳多种功能,光热转化效率较高。
Description
技术领域
本发明属复合材料技术领域,涉及一种铋掺杂的金属硫化物纳米花及其制备方法,具体地说是一种聚乙二醇等修饰的由单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼共同构成纳米花的花瓣的铋掺杂的金属硫化物纳米花及其制备方法。
背景技术
二维结构的过渡金属硫化物是由过渡族金属元素(M)和硫族非金属元素(X)组成的X-M-X类“三明治”结构的化合物,其制备方法大致包括机械剥离法、气相沉积法、水热合成法、插层剥离或液相剥离法等。由于金属硫化物尤其是过渡金属硫化物拥有许多独特的物理化学性质,如较大的比表面积和较强的近红外光吸收性能等,可用于肿瘤的药物递送和光热治疗,近年来层状金属硫化物得到了科研人员的广泛关注。目前,金属硫化物以MoS2和WS2的应用最为普遍,MoS2纳米片最先被报道用于光热治疗,WS2、ReS2纳米片也相继被报道用作有效的光热治疗试剂,TaS2和VS2纳米片还可用于生物成像引导治疗。
关于金属硫化物纳米材料的研究不少,专利CN109481679A报道了一种淋巴靶向硫化钼杂化纳米薄片的制备方法及其产品和应用,用水热合成法合成硫化钼,同时嵌入硫化物纳米粒子,增大了层与层的空间,更加有利于剥离;然后用有机溶剂作为反应溶剂,液相剥离硫化钼,制备二维硫化钼杂化纳米薄片;最后通过透明质酸修饰,制备了淋巴靶向的二维硫化钼杂化纳米薄片,该方法应用在临床癌症治疗中,可以实现对肿瘤细胞进行靶向光热治疗,避免杀伤正常细胞,但该发明采用液相剥离的方法,再用透明质酸进行修饰,制备工艺要求高,过程繁琐且复杂。专利CN108675267A报道了一种一步制备纳米金属硫化物及其复合物的通用方法,所述通用方法采用单质硫作为硫源,以草酸为还原剂,以金属氧化物或金属盐为金属源,水热合成纳米金属硫化物,该方法直接采用了硫粉作为硫源,无需使用有机硫作为硫源,成本更低,安全性更高,同时采用了性质稳定的草酸作为还原剂,以水为溶剂,仅需在相对温和的环境下进行制备,进一步提高了制备过程的安全性和降低了生产成本,但产物功能单一,应用受限。
但是结合金属硫化物和纳米花两者优势的,即基于金属硫化物纳米花的研究还不多。专利CN201110080921公开了一种硫化铜超结构及其在提高近红外光热转换效率中的应用,利用水热法制备出花状的CuS超结构,制备方法简单,结构稳定性好,而且材料价格低廉,这种超结构是由CuS片状纳米单元有序地排列组合而成,能够非常好地分散于水或者磷酸盐缓冲液(PBS)溶液中,它不仅自身在近红外区域有较强的吸收,而且由于超结构的多次内部反射作用,使其能够很好地吸收近红外光,因而使得光热转换效率有了很大的提高,但是该专利的“花状”超晶结构尺寸过大,难以临床转化;文献“Hydrophilic Cu9S5Nanocrystals:A Photothermal Agent with a 25.7%Heat Conversion Efficiency forPhotothermal Ablation of Cancer Cells in Vivo”中通过较为简便的热分解方法,合成出一种粒径在70nm左右的“盘状”Cu9S5纳米粒子,这个尺寸的纳米颗粒非常适合于癌症治疗,实验表明,该纳米粒子的光热转换效率高达25.7%,高于光热转换效率为23.7%的Au纳米棒。然而,这些金属硫化物材料还是存在一些局限:合成比较复杂、产率低、光热转换效率有限、功能单一、产物尺寸和形貌难以控制,以及产生较大的毒性等,而且现有的金属硫化物材料能实现多功能诊疗的也不多。
因此,研究一种合成简单、光热转化效率高且功能多样的基于金属硫化物的纳米花及其制备方法具有十分重要的意义。
发明内容
本发明的目的是解决现有技术中金属硫化物材料合成比较复杂、光热转换效率有限以及功能单一等问题,提供一种铋掺杂的金属硫化物纳米花及其制备方法。
为了达到上述目的,本发明采用的方案如下:
铋掺杂的金属硫化物纳米花的制备方法,将同时含有中间体粒子和四水硫代钼酸铵的溶液体系进行溶剂热反应制得铋掺杂的金属硫化物纳米花;中间体粒子是通过将A溶液和B溶液经过沉淀反应混合生成的,A溶液主要由BiCl3、MnCl2·4H2O和去离子水组成,B溶液主要由K4[Fe(CN)6]·3H2O、柠檬酸和去离子水组成。
本发明的铋掺杂的金属硫化物纳米花通过沉淀法和溶剂热反应法两个步骤被合成出来,反应过程较为简便,反应过程中调控反应温度和时间,确定合适的反应条件即可得到预想的铋掺杂的金属硫化物纳米花的尺寸和形貌,纳米花粒子可通过近红外激光照射和pH调控化疗药物在肿瘤部位的释放,实现包括增敏的计算机断层扫描(CT)成像、光声(PA)成像、磁共振(MR)成像在内的多模成像功能,还能够在激光照射下激发光热治疗与光动力治疗使肿瘤细胞消融。这种新型“花状”纳米材料,集多功能于一个性能突出的诊疗平台上,实现多模成像诊断与治疗协同的诊疗一体化,对癌症诊疗研究与临床应用提出了新的思路和方向。
作为优选的技术方案:
如上所述的铋掺杂的金属硫化物纳米花的制备方法,所述溶液体系中还含有修饰剂,加入修饰剂是为了提高生物相容性,所述修饰剂为聚乙二醇、聚乙烯亚胺、聚赖氨酸、壳聚糖、透明质酸钠或海藻酸钠,所述修饰剂的相对分子质量为1000~10000,若修饰剂的相对分子质量过高,可能会产生额外的毒性;若修饰剂的相对分子量过低,可能无法有效包裹住纳米花。
如上所述的铋掺杂的金属硫化物纳米花的制备方法,具体步骤如下:
(1)将BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成A溶液;将K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成B溶液;
(2)将B溶液逐滴加入A溶液中,保持温度并剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,清洗,收集中间体粒子并干燥,其中剧烈搅拌的搅拌速度为600rpm以上,由于A溶液和B溶液混合以后发生沉淀反应,沉淀反应非常迅速,若不进行剧烈搅拌容易使制备得到的中间体粒子大小不均一;A溶液和B溶液的比例无特殊要求,只要保证总体积小于水热反应釜所能容纳的体积即可;
(3)将中间体粒子、四水硫代钼酸铵和修饰剂共同溶解于DMF、DMA、乙二醇、二甲亚砜或N,N-二甲基苯胺中形成所述溶液体系,并进行超声处理,使材料充分溶解于溶剂;
(4)进行溶剂热反应生成铋掺杂的金属硫化物纳米花;
(5)清洗,收集铋掺杂的金属硫化物纳米花并干燥。如上所述的铋掺杂的金属硫化物纳米花的制备方法,步骤(1)中,为了形成期望大小的中间体粒子并得到综合性能较高的产物,A溶液的质量浓度为10~15mg/mL,BiCl3与MnCl2·4H2O的摩尔比为0.9~1.1:0.9~1.1;B溶液的质量浓度为10~15mg/mL,K4[Fe(CN)6]·3H2O与柠檬酸的摩尔比为0.9~1.1:0.9~1.1。
如上所述的铋掺杂的金属硫化物纳米花的制备方法,步骤(2)中,逐滴加入之前,将A溶液和B溶液加热到50~80℃,并对A溶液和B溶液进行磁力搅拌。
如上所述的铋掺杂的金属硫化物纳米花的制备方法,步骤(3)中,中间体粒子、四硫代钼酸铵和修饰剂的质量比为2.5~3.5:0.8~1.2:0.8~1.2;溶液体系的质量浓度为1.5~2.5mg/mL;超声处理的频率为20~50kHz,时间为5~15min。如上所述的铋掺杂的金属硫化物纳米花的制备方法,步骤(4)中,溶剂热反应条件:温度为210~240℃,温度过高或过低生成的纳米花粒径形貌都有所差异;时间为6~16h,若溶液热反应的时间较长,会导致纳米花成为碎片。如上所述的铋掺杂的金属硫化物纳米花的制备方法,步骤(2)和步骤(5)中,清洗是指先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态;收集采用离心收集的方式,离心转速为8000~12000rpm,离心时间为10~20min,过低的离心转速以及过短的离心时间均可能导致产物收集不完全;干燥是指在温度为50~70℃且真空度为5~100Pa的条件下真空干燥24~48h。
如上任一项所述的铋掺杂的金属硫化物纳米花的制备方法制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片。
如上所述的铋掺杂的金属硫化物纳米花,纳米花的表面包裹有修饰剂,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.5~4.0:1.5~1.8:0.8~1.2:0.8~1.2;铋掺杂的金属硫化物纳米花的光热转换效率为50%~55%,对DOX(即阿霉素)的负载率为89%~92%,粒径为100~140nm。
有益效果:
(1)本发明的铋掺杂的金属硫化物纳米花制备过程简单,成本较低,产物粒径120nm左右,与专利CN109125735A报道的Mn-DOX载药治疗体系的粒径(100nm)相当,可以通过体内正常代谢作用排出体外,应用前景广阔;
(2)本发明制得的铋掺杂的金属硫化物纳米花能够实现单一结构容纳多种功能,非常适合于药物输送;
(3)本发明制得的铋掺杂的金属硫化物纳米花有较高的DOX负载率(约为90.0%),与专利CN109568330A报道的二硫化钼纳米载药复合物的最高载药效率94.43%相当,且本发明的纳米花具有pH响应的和近红外光可控的药物释放性能;
(4)本发明制得的铋掺杂的金属硫化物纳米花具有优异的光热转换效率(经计算,其光热转换效率可达54.7%),高于很多Bi基或过渡金属基硫化物的光热材料,如Bi-PEG纳米晶(~30.1%)2、Bi-SR-PEG纳米粒子(~45.3%)3、MoS2纳米片(~24.37%)4等;在安全功率密度(1.0W/cm2)的808nm激光照射下,能有效的将近红外激光的能量转换成热量杀死癌细胞进行光热治疗,还可实现光热治疗、光动力治疗与化疗协同的联合治疗;此外,还具有潜在的放射性治疗应用;
(5)本发明制得的铋掺杂的金属硫化物纳米花同时也是优良的生物成像造影剂,可实现增敏的计算机断层扫描(CT)成像、光声(PA)成像、T1加权的磁共振(MR)成像在内的多模成像功能;
(6)本发明制得的铋掺杂的金属硫化物纳米花具有良好的生物相容性。
附图说明
图1和图2为本发明的Bi-MSX-PEG纳米花的不同放大倍数的TEM图;
图3为本发明的Bi-MSX-PEG纳米花的体外实验的光热性能图;
图4为本发明的Bi-MSX-PEG纳米花的升温图;
图5为本发明的Bi-MSX-PEG纳米花的光动力性能测试图;
图6为本发明的Bi-MSX-PEG纳米花的药物缓释曲线图;
图7为本发明的Bi-MSX-PEG纳米花的T1加权像图;
图8为本发明的Bi-MSX-PEG纳米花的r1弛豫率图;
图9为本发明的Bi-MSX-PEG纳米花的CT成像图;
图10为本发明的Bi-MSX-PEG溶液和碘海醇溶液在CT成像下的HU值对比图;
图11为CCK-8法测定HeLa细胞与不同浓度的本发明的Bi-MSX-PEG溶液共培养24小时后的细胞存活率图;
图12为体内治疗实验中各组小鼠相对肿瘤体积随时间变化的趋势图。
具体实施方式
下面结合具体实施方式,进一步阐述本发明。应理解,这些实施例仅用于说明本发明而不用于限制本发明的范围。此外应理解,在阅读了本发明讲授的内容之后,本领域技术人员可以对本发明作各种改动或修改,这些等价形式同样落于本申请所附权利要求书所限定的范围。
实施例1
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为0.9:0.9的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为10mg/mL的A溶液;将摩尔比为0.9:0.9的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为10mg/mL的B溶液;
(2)将A溶液和B溶液加热到50℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以600rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为8000rpm,离心时间为20min,在温度为50℃且真空度为5Pa的条件下真空干燥48h;
(4)将质量比为2.5:0.8:0.8的中间体粒子、四水硫代钼酸铵和相对分子质量为1000的聚乙二醇共同溶解于DMF中形成质量浓度为1.5mg/mL的溶液体系,并进行超声处理,超声处理的频率为20kHz,时间为15min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为210℃,时间为12h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为8000rpm,离心时间为20min,在温度为50℃且真空度为5Pa的条件下真空干燥48h。
最终制得的铋掺杂的金属硫化物纳米花(Bi-MSX-PEG纳米花),为纳米片之间相互缠绕和扭结形成的纳米花状结构,其不同放大倍数的TEM图分别如图1和图2所示,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有聚乙二醇,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.5:1.5:0.8:0.8;铋掺杂的金属硫化物纳米花的光热转换效率为50%,对DOX的负载率为89%,粒径为100nm。
对Bi-MSX-PEG纳米花进行体外实验,测试Bi-MSX-PEG纳米花的光热性能,我们通过激光照射Bi-MSX-PEG溶液来研究材料的光热转换能力。其测试结果如图3所示,不同浓度的Bi-MSX-PEG水溶液(25μg·mL-1、50μg·mL-1、100μg·mL-1、200μg·mL-1和400μg·mL-1)在NIR激光照射(808nm,1.0W·cm-2)下的时间-温度变化曲线,在5分钟内溶液温度最高可提升至73.9℃以上。各浓度溶液在激光照射下5分钟内温度均出现不同程度的提升,如图4所示,温度提升值分别为6.4℃、8.9℃、13.5℃、28.7℃和50.5℃(升温效应与浓度基本呈正相关关系),而纯水的对照组升温则非常不明显,仅上升约1.2℃。证明本发明的Bi-MSX-PEG纳米花光热转换性能较强。浓度低至25μg·mL-1时即可对肿瘤产生较大杀伤作用(肿瘤局部高于42℃即可杀死癌细胞)。
测试Bi-MSX-PEG纳米花的光动力性能,评估其在激光照射下产生活性氧自由基(ROS)的能力。1,3-二苯基异苯并呋喃(DPBF)是一种化学捕获试剂,它可以与1O2发生不可逆反应,反应后生成的新物质会减弱DPBF在410nm的吸收峰。测试得到的Bi-MSX-PEG纳米花的光动力性能测试图如图5所示,图中出现的(1)、(2)、(3)、(4)、(5)、(6)和(7)分别代表Bi-MSX-PEG纳米花在激光照射时间为0min、2min、4min、6min、8min、10min和15min产生的1O2与DPBF作用后的紫外光吸收图谱,由图可知,Bi-MSX-PEG溶液经激光照射超过4分钟后,溶液在410nm的吸收峰开始出现明显减弱,表明Bi-MSX-PEG纳米花在NIR照射下能够有效产生1O2,也说明材料适合用于光动力治疗试剂。证明本发明的Bi-MSX-PEG纳米花作为性能突出的光敏剂,非常适合于光热治疗和光动力治疗。
测试Bi-MSX-PEG纳米花的药物响应释放性能,我们把Bi-MSX-PEG/DOX纳米复合物分别分散在pH=5.0(癌细胞和溶酶体pH的平均值)和pH=7.4(正常生理环境下的pH值)的PBS缓冲液中,两种pH溶液的激光组每小时使用近红外激光照射5分钟(808nm,1.0W/cm2),对照组不用近红外光照射。测试得到的Bi-MSX-PEG纳米花的药物缓释曲线图如图6所示,图中pH 7.4、pH 7.4+NIR、pH 5.0、pH 5.0+NIR分别代表Bi-MSX-PEG纳米花在pH=7.4无激光照射的条件下、pH=7.4有激光照射的条件下、pH=5.0无激光照射的条件下、pH=5.0有激光照射的条件下的药物释放情况,在pH=7.4无激光照射的条件下,DOX在10小时内的累积释放量约为20.0%,然而在pH=5.0且有激光照射的条件下,DOX在10小时内的累计释放量可达80.0%。证明本发明的Bi-MSX-PEG纳米花可实现对pH和近红外光响应的促进或控制DOX释放。
测试Bi-MSX-PEG纳米花的磁共振成像性能。经测试得到的Bi-MSX-PEG纳米花的T1加权像图如图7所示,由图可知,随着Bi-MSX-PEG溶液中Mn离子浓度的增加,在T1加权模式下,MR对比图像变得越来越亮。而且,经测试得到的Bi-MSX-PEG纳米花r1的弛豫率图如图8所示,由图可知纳米花的弛豫率r1为2.60mM-1s-1。证明本发明的Bi-MSX-PEG纳米花适用于T1加权的核磁共振造影剂。
测试Bi-MSX-PEG纳米花的CT成像性能。含有High-Z元素X射线衰减试剂通常可以实现增强的CT成像,Bi就属于拥有较高X射线衰减系数的High-Z元素。通过不同浓度的Bi-MSx-PEG溶液测试纳米花的CT体外成像性能。测试得到的Bi-MSX-PEG纳米花的CT成像图如图9所示,随着Bi浓度的增加,Bi-MSX-PEG溶液的CT图像出现明显的信号增强过程。其次,测试得到的Bi-MSX-PEG溶液(图中用Bi代表)和碘海醇溶液(图中用I代表)在CT成像下的HU值对比图如图10所示,由图可知纳米花溶液的HU斜率值(≈2.82HU·mM-1)要高于临床常用CT成像对比试剂——碘海醇(≈2.26HU·mM-1)。证明本发明的Bi-MSX-PEG纳米花在CT增强成像方面具有广阔的应用前景。
测试Bi-MSX-PEG纳米花的生物相容性。将HeLa细胞与含有不同浓度(从1.56μg·mL-1到200μgmL-1)Bi-MSx-PEG纳米粒子的培养基共培养24h,然后利用CCK-8法测定细胞存活率。测试得到HeLa细胞与不同浓度Bi-MSX-PEG纳米花共培养24小时后的细胞存活率如图11所示,由图可知,材料浓度高达200μg·mL-1的情况下,对应的细胞存活率仍高于90%,证明本发明的Bi-MSX-PEG纳米花对细胞毒性是非常低的。
测试Bi-MSX-PEG纳米花的体内联合治疗性能,测试得到的体内治疗实验中各组小鼠相对肿瘤体积随时间变化的趋势图如图12所示,图中Control、NIR、DOX、Bi-MSX-PEG、Bi-MSX-PEG+NIR、Bi-MSX-PEG/DOX、Bi-MSX-PEG/DOX+NIR分别代表治疗期间各组小鼠未接受任何治疗方式处理、接受近红外激光治疗、接受DOX治疗、接受Bi-MSX-PEG治疗、接受近红外激光治疗和Bi-MSX-PEG治疗、接受Bi-MSX-PEG治疗和DOX治疗、接受Bi-MSX-PEG治疗和DOX治疗和近红外激光治疗后其肿瘤部位的体积生长变化情况,由图可知,对照组、NIR组和Bi-MSX-PEG组的肿瘤在治疗期间持续增殖,说明近红外激光和Bi-MSX-PEG纳米材料本身均不能对肿瘤产生杀伤作用,无法抑制肿瘤生长。Bi-MSX-PEG/DOX组和单独DOX组在治疗前期对肿瘤生长产生轻微抑制作用,但随之而来的仍然是快速的增殖,这很可能是基于对化疗药物毒副作用的考虑而限制了其剂量,导致治疗效果不佳。Bi-MSX-PEG+NIR组的小鼠肿瘤得到有效抑制,不过治疗后期组内小鼠出现了肿瘤再生的情况。然而,获得多模联合治疗(化疗、PTT和PDT三种治疗模式协同)的Bi-MSX-PEG/DOX+NIR组则展现出十分优异的治疗效果,小鼠肿瘤在10天内被完全清除,后期未出现肿瘤复发、再生的情况,比单独的化疗、以及光热与光动力协同治疗组的治疗效率都要更高。证明本发明的Bi-MSX-PEG纳米花的体内联合治疗的十分优异。
实施例2
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为1.1:1.1的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为15mg/mL的A溶液;将摩尔比为1.1:1.1的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为15mg/mL的B溶液;
(2)将A溶液和B溶液加热到80℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以650rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为12000rpm,离心时间为10min,在温度为70℃且真空度为100Pa的条件下真空干燥24h;
(4)将质量比为3.5:1.2:1.2的中间体粒子、四水硫代钼酸铵和相对分子质量为10000的聚乙烯亚胺共同溶解于DMA中形成质量浓度为2.5mg/mL的溶液体系,并进行超声处理,超声处理的频率为50kHz,时间为5min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为240℃,时间为8h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为12000rpm,离心时间为10min,在温度为70℃且真空度为100Pa的条件下真空干燥24h。
最终制得的铋掺杂的金属硫化物纳米花(Bi-MSX-PEG),为纳米片之间相互缠绕和扭结形成的纳米花状结构,图1和图2分别为XX和XX倍数的TEM图,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有聚乙烯亚胺,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为4.0:1.8:1.2:1.2;铋掺杂的金属硫化物纳米花的光热转换效率为55%,对DOX的负载率为92%,粒径为140nm。
实施例3
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为1.0:1.0的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为12mg/mL的A溶液;将摩尔比为1.0:1.0的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为12mg/mL的B溶液;
(2)将A溶液和B溶液加热到60℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以700rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为9000rpm,离心时间为18min,在温度为60℃且真空度为20Pa的条件下真空干燥42h;
(4)将质量比为3.0:1.0:1.0的中间体粒子、四水硫代钼酸铵和相对分子质量为2000的聚赖氨酸共同溶解于乙二醇中形成质量浓度为1.8mg/mL的溶液体系,并进行超声处理,超声处理的频率为30kHz,时间为12min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为220℃,时间为16h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为9000rpm,离心时间为18min,在温度为60℃且真空度为20Pa的条件下真空干燥42h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有聚赖氨酸,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.8:1.6:0.9:1.0;铋掺杂的金属硫化物纳米花的光热转换效率为52%,对DOX的负载率为90%,粒径为120nm。
实施例4
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为0.9:1.1的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为12mg/mL的A溶液;将摩尔比为0.9:1.1的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为12mg/mL的B溶液;
(2)将A溶液和B溶液加热到70℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以800rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为10000rpm,离心时间为15min,在温度为60℃且真空度为50Pa的条件下真空干燥35h;
(4)将质量比为2.5:1.2:0.8的中间体粒子、四水硫代钼酸铵和相对分子质量为5000的壳聚糖共同溶解于二甲亚砜中形成质量浓度为2.0mg/mL的溶液体系,并进行超声处理,超声处理的频率为40kHz,时间为8min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为220℃,时间为14h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为11000rpm,离心时间为12min,在温度为60℃且真空度为80Pa的条件下真空干燥30h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有壳聚糖,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.6:1.7:0.9:1.0;铋掺杂的金属硫化物纳米花的光热转换效率为52%,对DOX的负载率为90%,粒径为135nm。
实施例5
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为1.0:0.9的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为14mg/mL的A溶液;将摩尔比为1.0:1.1的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为11mg/mL的B溶液;
(2)将A溶液和B溶液加热到70℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以900rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为8000rpm,离心时间为20min,在温度为70℃且真空度为90Pa的条件下真空干燥48h;
(4)将质量比为3.5:0.8:1.0的中间体粒子、四水硫代钼酸铵和相对分子质量为8000的透明质酸钠共同溶解于N,N-二甲基苯胺中形成质量浓度为2.5mg/mL的溶液体系,并进行超声处理,超声处理的频率为50kHz,时间为5min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为220℃,时间为15h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为8000rpm,离心时间为20min,在温度为70℃且真空度为90Pa的条件下真空干燥40h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有透明质酸钠,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为4.0:1.8:0.8:1.0;铋掺杂的金属硫化物纳米花的光热转换效率为55%,对DOX的负载率为91%,粒径为120nm。
实施例6
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为0.9:1.0的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为13mg/mL的A溶液;将摩尔比为1.1:0.9的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为10mg/mL的B溶液;
(2)将A溶液和B溶液加热到70℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以600rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为12000rpm,离心时间为10min,在温度为70℃且真空度为5Pa的条件下真空干燥48h;
(4)将质量比为3.0:1.0:1.2的中间体粒子、四水硫代钼酸铵和相对分子质量为1000的海藻酸钠共同溶解于N,N-二甲基苯胺中形成质量浓度为1.9mg/mL的溶液体系,并进行超声处理,超声处理的频率为50kHz,时间为5min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为240℃,时间为6h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为12000rpm,离心时间为10min,在温度为60℃且真空度为50Pa的条件下真空干燥24h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有海藻酸钠,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.5:1.5:1.0:1.0;铋掺杂的金属硫化物纳米花的光热转换效率为55%,对DOX的负载率为89%,粒径为140nm。
实施例7
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为0.9:0.9的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为15mg/mL的A溶液;将摩尔比为1.1:1.1的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为10mg/mL的B溶液;
(2)将A溶液和B溶液加热到80℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以1000rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为8000rpm,离心时间为20min,在温度为50℃且真空度为100Pa的条件下真空干燥48h;
(4)将质量比为3.5:0.8:0.8的中间体粒子、四水硫代钼酸铵和相对分子质量为7000的聚乙二醇共同溶解于DMF中形成质量浓度为2.5mg/mL的溶液体系,并进行超声处理,超声处理的频率为50kHz,时间为5min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为240℃,时间为6h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速12000rpm,离心时间为10min,在温度为50℃且真空度为5Pa的条件下真空干燥40h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有聚乙二醇,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.5:1.8:1.2:1.1;铋掺杂的金属硫化物纳米花的光热转换效率为50%,对DOX的负载率为89%,粒径为100nm。
实施例8
铋掺杂的金属硫化物纳米花的制备方法,其具体步骤如下:
(1)将摩尔比为1.0:1.1的BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成质量浓度为15mg/mL的A溶液;将摩尔比为1.1:1.1的K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成质量浓度为10mg/mL的B溶液;
(2)将A溶液和B溶液加热到80℃,并对A溶液和B溶液进行磁力搅拌;
(3)将B溶液逐滴加入A溶液中,保持温度并以700rpm的搅拌速度剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集中间体粒子,离心转速为8000rpm,离心时间为20min,在温度为65℃且真空度为75Pa的条件下真空干燥25h;
(4)将质量比为3.5:0.8:0.8的中间体粒子、四水硫代钼酸铵和相对分子质量为1000的聚乙烯亚胺共同溶解于DMA中形成质量浓度为2.5mg/mL的溶液体系,并进行超声处理,超声处理的频率为50kHz,时间为5min;
(5)进行溶剂热反应生成铋掺杂的金属硫化物纳米花,溶剂热反应的温度为240℃,时间为6h;
(6)先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态,采用离心收集的方式收集铋掺杂的金属硫化物纳米花,离心转速为12000rpm,离心时间为10min,在温度为70℃且真空度为100Pa的条件下真空干燥24h。
最终制得的铋掺杂的金属硫化物纳米花,为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片;纳米花的表面包裹有聚乙烯亚胺,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为4.0:1.5:1.2:0.8;铋掺杂的金属硫化物纳米花的光热转换效率为50%,对DOX的负载率为89%,粒径为100nm。
Claims (10)
1.铋掺杂的金属硫化物纳米花的制备方法,其特征是:将同时含有中间体粒子和四水硫代钼酸铵的溶液体系进行溶剂热反应制得铋掺杂的金属硫化物纳米花;
中间体粒子是通过将A溶液和B溶液混合生成的,A溶液主要由BiCl3、MnCl2·4H2O和去离子水组成,B溶液主要由K4[Fe(CN)6]·3H2O、柠檬酸和去离子水组成。
2.根据权利要求1所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,所述溶液体系中还含有修饰剂,所述修饰剂为聚乙二醇、聚乙烯亚胺、聚赖氨酸、壳聚糖、透明质酸钠或海藻酸钠,所述修饰剂的相对分子质量为1000~10000。
3.根据权利要求2所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,具体步骤如下:
(1)将BiCl3与MnCl2·4H2O共同溶解于去离子水中,形成A溶液;将K4[Fe(CN)6]·3H2O与柠檬酸共同溶解于去离子水中,形成B溶液;
(2)将B溶液逐滴加入A溶液中,保持温度并剧烈搅拌,溶液颜色逐渐变为亮绿色后,自然冷却至室温,清洗,收集中间体粒子并干燥,其中剧烈搅拌的搅拌速度为600rpm以上;
(3)将中间体粒子、四水硫代钼酸铵和修饰剂共同溶解于DMF、DMA、乙二醇、二甲亚砜或N,N-二甲基苯胺中形成所述溶液体系,并进行超声处理;
(4)进行溶剂热反应生成铋掺杂的金属硫化物纳米花;
(5)清洗,收集铋掺杂的金属硫化物纳米花并干燥。
4.根据权利要求3所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,步骤(1)中,A溶液的质量浓度为10~15mg/mL,BiCl3与MnCl2·4H2O的摩尔比为0.9~1.1:0.9~1.1;B溶液的质量浓度为10~15mg/mL,K4[Fe(CN)6]·3H2O与柠檬酸的摩尔比为0.9~1.1:0.9~1.1。
5.根据权利要求3所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,步骤(2)中,逐滴加入之前,将A溶液和B溶液加热到50~80℃,并对A溶液和B溶液进行磁力搅拌。
6.根据权利要求3所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,步骤(3)中,中间体粒子、四硫代钼酸铵和修饰剂的质量比为2.5~3.5:0.8~1.2:0.8~1.2;溶液体系的质量浓度为1.5~2.5mg/mL;超声处理的频率为20~50kHz,时间为5~15min。
7.根据权利要求3所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,步骤(4)中,溶剂热反应条件:温度为210~240℃,时间为6~16h。
8.根据权利要求3所述的铋掺杂的金属硫化物纳米花的制备方法,其特征在于,步骤(2)和步骤(5)中,清洗是指先用乙醇清洗3次,再用去离子水清洗3次,直至离心后的上清液为无色澄清状态;收集采用离心收集的方式,离心转速为8000~12000rpm,离心时间为10~20min;干燥是指在温度为50~70℃且真空度为5~100Pa的条件下真空干燥24~48h。
9.采用如权利要求1~8任一项所述的铋掺杂的金属硫化物纳米花的制备方法制得的铋掺杂的金属硫化物纳米花,其特征是:为纳米片之间相互缠绕和扭结形成的纳米花状结构,纳米片是单质铋、硫化铋、硫化锰、硫化亚铁和硫化钼通过二维结构上的相互取代和镶嵌得到的掺杂型金属硫化物纳米片。
10.根据权利要求9所述的铋掺杂的金属硫化物纳米花,其特征在于,纳米花的表面包裹有修饰剂,二者通过静电和物理吸附作用连接;铋掺杂的金属硫化物纳米花中各金属元素的含量比Bi:Fe:Mn:Mo为3.5~4.0:1.5~1.8:0.8~1.2:0.8~1.2;铋掺杂的金属硫化物纳米花的光热转换效率为50%~55%,对DOX的负载率为89%~92%,粒径为100~140nm。
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