CN107158378A - 一种光热效应用硫化铜锰蛋白复合纳米颗粒及其制备方法 - Google Patents
一种光热效应用硫化铜锰蛋白复合纳米颗粒及其制备方法 Download PDFInfo
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Abstract
本发明属于光热治疗纳米复合材料的制备领域，特指一种光热效应用硫化铜锰蛋白复合纳米材料及其制备方法。以深绿色的柠檬酸盐包裹的硫化铜纳米晶体溶液为原料，加入二价锰离子(Mn2+)及氟硼吡咯取代的二吡啶甲基胺(PDA)与纳米硫化铜纳米晶体表面组装，再运用PEG‑FA‑COOH修饰的牛血清白蛋白(BSA)包裹的方法，成功合成了具有较高光热转换效率的新型硫化铜锰蛋白复合纳米颗粒。其制备可获得多功能肿瘤诊疗的无机纳米光热试剂，可解决肿瘤光热治疗时光热效应较低问题，是一种低毒性、生物相容性和肿瘤靶向性的多功能磁共振成像和光激发细胞荧光成像引导的光热诊疗剂。
Description
技术领域
本发明属于光热治疗纳米复合材料的制备领域，特指一种光热效应用硫化铜锰蛋白复合纳米材料及其制备方法。
背景技术
光热治疗是利用电磁辐射的方式治疗包括癌症在内的各种疾病，它具有非侵入性、副作用小以及对正常组织不会造成热损伤的优点。其中，硫化铜纳米颗粒在光热治疗中具有潜在的应用。与贵金属纳米材料，半导体纳米材料和碳基纳米材料相比，硫化铜纳米颗粒具有成本低、毒性低、可生物降解、光稳定性好、近红外宽波段吸收强和良好的光电转换性能等优点。但是，由于硫化铜纳米颗粒生物相容性低和缺乏肿瘤靶向性能，限制了其在分子成像和肿瘤光热诊疗上的应用(Liwen Zhang and Shi Gao.Activatable hyaluronicacid nanoparticle as a theranostic agent for optical/photoacoustic image-guided photothermal therapy.ACS nano.2014,8(12):12250-12258.)。通过生物矿化的概念，使用天然的生物聚合物，比如：铁蛋白(Fn)为模板，成功合成了硫化铜纳米簇，在一定程度上改善了硫化铜纳米颗粒的分散性，但缺乏肿瘤靶向性(Biomineralization-inspired synthesis of copper sulfide-ferritin nanocages as cancertheranostics.ACS Nano 2016,10,3453-3460.)。
近红外光的范围在700-900nm(如808nm)是皮肤和组织的最低程度吸收，有较深(达到10cm)的组织穿透力(Zhang,Z.；Wang,J.；Chen,C.Near-infrared light-mediatednanoplatforms for cancer thermo-chemotherapy and opticalimaging.Adv.Mater.2013,25(28),3869-3880.)。近红外光介导的光热治疗是抗肿瘤治疗的新型模式，将吸收的近红外光转换为热能，从而有效的破坏肿瘤细胞。众所周知，细胞对周围环境的温度敏感，因此，光激发促使局部区域温度过高(超过42℃)可以杀死肿瘤细胞，且对周围正常组织和细胞成分不造成损伤(Cheng,L.；Wang,C.；Feng,L.；Yang,K.；Liu,Z.Functional nanomaterials for phototherapies of cancer.Chem.Rev.2014,114,10869-10939.)。
目前，光热治疗试剂主要分为有机和无机光热试剂，但是大多数有机光热试剂仅在紫外/可见光处可激活和易于光漂白，限制了它们的应用。碳纳米管和氧化石墨烯光热转换效率低，无机光热试剂如基于Au纳米材料在NIR光照射下光稳定性低(Wang,D.G.；Xu,Z.A.；et al.Treatment of metastatic breast cancer by combination ofchemotherapy and photothermal ablation using doxorubicin-loaded DNA wrappedgold nanorods.Biomaterials 2014,35(29),8374-8384.)。因此，近红外光强吸收和光稳定性高的硫化铜锰蛋白复合纳米材料的制备可获得多功能肿瘤诊疗的无机纳米光热试剂，可解决肿瘤光热治疗时光热效应较低问题，是一种低毒性、生物相容性和肿瘤靶向性的多功能磁共振成像和光激发细胞荧光成像引导的光热诊疗剂。
发明内容
本发明设计了一种新型的硫化铜锰蛋白复合纳米颗粒：PDAMn-CuS@BSA-FA。以深绿色的柠檬酸盐包裹的硫化铜纳米晶体溶液为原料，加入二价锰离子(Mn2+)及氟硼吡咯取代的二吡啶甲基胺(PDA)与纳米硫化铜纳米晶体表面组装，再运用PEG-FA-COOH修饰的牛血清白蛋白(BSA)包裹的方法，成功合成了具有较高光热转换效率的新型硫化铜锰蛋白复合纳米颗粒。这种PDAMn-CuS@BSA-FA复合纳米颗粒的水溶液，在测试光热效应时，设置激发光源功率为2W/cm2，得到在近红外光(808nm)照射下，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(配制浓度为400μg mL-1)的温度在10min(600s)内增加了44.7℃(空白：水的温度变化ΔT＝8.8℃)，PDAMn-CuS@BSA-FA复合纳米颗粒的粒径大小为20nm。其紫外-可见光区的特征吸收分别在499nm(PDA特征吸收)和900-1000nm(CuS特征吸收)处。
一种光热效应用硫化铜锰纳米颗粒的制备方法，按照下述步骤进行：
硫化铜的制备按照文献中报道的方法(M.Zhou,R.Zhang,M.Huang,W.Lu,S.Song,M.P.Melancon,M.Tian,D.Liang and C.Li.A chelator-free multifunctional[64Cu]-CuSnanoparticle platform for simultaneous micro-PET/CT imaging and photothermalablation therapy.J.Am.Chem.Soc.,2010,132,15351-15358.)，以纳米硫化铜为模板，在深绿色的柠檬酸盐包裹的硫化铜纳米晶体溶液中加入氯化锰(MnCl2·4H2O)溶液，混合均匀后放置在平台搅拌器上，第一次室温搅拌后将溶液转移到水浴中，缓慢滴加有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液与Mn2+配位，20-70℃加热20-60min；缓慢降至室温；逐滴滴加生物大分子蛋白BSA-PEG-FA的水溶液控制形成均一纳米颗粒，转移到平台搅拌器上，第二次室温搅拌后加入丙酮使纳米颗粒沉降，静置8-12h后得到PDAMn-CuS@BSA-FA复合纳米颗粒。将纳米颗粒重新分散在去离子水中，即可得到具有增强光热效应的新型硫化铜锰蛋白复合纳米颗粒水溶液(PDAMn-CuS@BSA-FA)，C CuS＝400μg mL-1。
所述第一次室温搅拌的时间为5-15min，优选10min。
所述加热温度为70℃，加热时间为30min。
所述降温时间为10-20min，最佳15min。
所述第二次室温搅拌时间为3-5h，最佳4h。
所述静置时间为10h。
其中所述的硫化铜纳米晶体水溶液的浓度为0.1mg mL-1，MnCl2·4H2O溶液的浓度为248mM，每1mL柠檬酸盐包裹的硫化铜纳米颗粒表面有2.04μmol羧基(CuS-COO-)。
其中所述的CuS-COO-与Mn2+的摩尔比为3:1-2:3，最佳摩尔比为2:1。
其中所述的氟硼吡咯取代的二吡啶甲基胺(PDA)与Mn2+的摩尔比为1:1-1:30，最佳摩尔比为1:29.52。
其中所述的BSA-PEG-FA与Mn2+的摩尔比为1:1000-1:2000，最佳摩尔比为1:1653。
文献中硫化铜光热治疗纳米材料已有报道，在中国专利201510217271.7“一种生物相容性良好的CuS光热治疗纳米材料的制备方法”中，采用一锅法以生物大分子为模板控制粒径构建光热纳米材料，改善了硫化铜的生物相容性，但是光热转换效率低；本发明首次制备了含有二价锰离子与BSA-PEG-FA的硫化铜纳米颗粒，通过引入有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)与二价锰离子配位作用增强了硫化铜的光热转换效应，运用生物大分子蛋白BSA-PEG-FA的包裹作用，获得BSA-PEG-FA为壳，PDAMn-CuS为核的生物相容性的复合纳米颗粒(图1)，核壳结构的硫化铜锰蛋白(PDAMn-CuS@BSA-FA)复合纳米颗粒(图2)具有近红外区域强吸收和高效的光热效应(图3)；且在模拟生物环境中，发现PDAMn-CuS@BSA-FA复合纳米颗粒水溶液在近红外激发光(808nm)激发后与生物大分子蛋白作用进而释放有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)，可运用于肿瘤细胞荧光成像；此外，二价锰离子提供了磁共振成像的性能。这种利用有机荧光配体与金属的相互作用提高硫化铜纳米颗粒的光热效应的方法为首次报道。
附图说明
图1为PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的紫外吸收图谱。a，44μM，乙腈、b，纳米CuS(b，0.1mg/mL，水)和c，纳米PDAMn-CuS@BSA-FA(c，C CuS＝0.1mg mL-1，水)的紫外可见光光谱。
图2为核壳结构的PDAMn-CuS@BSA-FA复合纳米颗粒的TEM图。
图3为不同浓度PDAMn-CuS@BSA-FA复合纳米颗粒水溶液在近红外激光(808nm，功率为2W/cm2)照射下的温度随时间变化图。
图1，2和3分别是实施例1制备的PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的紫外吸收光谱，透射电镜图和光热效应图。从紫外光谱中看出明显的有机配体PDA(499nm)和CuS(800-1000nm)的特征吸收峰；从透射电镜图看出纳米颗粒尺寸均一，粒径大小约为20nm，有明显的蛋白包裹的核壳结构；且在近红外激发光(808nm，功率为2W/cm2)的照射下，10min内PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了44.7℃，计算其光热转换效率达到66.02％。
具体实施方式
试剂与仪器：本发明所用的溶剂皆为分析纯，所用试剂未加特殊说明直接应用而未经任何特殊处理。
CuCl2·2H2O(分析纯，上海试剂四厂)，Na2S·9H2O(分析纯，上海统亚化工科技发展有限公司)，NaOH(分析纯，上海化学试剂有限公司)，柠檬酸钠(国药集团化学试剂有限公司)，乙醇(分析纯，国药集团化学试剂有限公司)，乙腈(分析纯，国药集团化学试剂有限公司)，BSA(国药集团化学试剂有限公司)，FA-PEG-COOH(上海芃硕生物科技有限公司)，MnCl2·4H2O(分析纯，国药集团化学试剂有限公司)。
紫外可见分光光度仪(日本岛津UV-2450型)，190-1100nm；Carry Eclipse荧光分光光度计(美国瓦里安有限公司)；JEM-200CX型透射电镜(日本电子株式会社)；DHG-9140A型电热恒温鼓风干箱(上海-恒科技有限公司)；DZF-6051型真空干燥箱(上海-恒科技有限公司)；TopPette手动单道可调式移液枪(20-200μL)；恒温水浴锅(巩义市予华仪器有限公司)。硫化铜水溶液根据文献报道的方法合成。
具体实施方案
实施例1(PDAMn-CuS@BSA-FA最佳制备方案)
以制备的硫化铜水溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)为模板，在72mL深绿色的柠檬酸盐包裹的硫化铜纳米晶体水溶液中加入300μL氯化锰(MnCl2·4H2O，248mM)溶液，混合均匀后放置在平台搅拌器上，室温搅拌10min(溶液中可见析出的深绿色颗粒)；将溶液转移到水浴中，缓慢滴加300μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)，有机荧光配体PDA与Mn2+配位，升温至70℃，继续加热反应30min，形成稳定的配合物包裹的CuS纳米颗粒；反应结束后，缓慢降温至室温，降温时间为15min；将溶液转移至平台搅拌器上，逐滴滴加888μL BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，即可得到稳定的蛋白包裹的核壳结构的硫化铜锰蛋白纳米颗粒；后加入丙酮使纳米颗粒沉降，静置10h，将纳米颗粒重新分散在3mL去离子水溶液中，即可得到具有较高光热效应的新型硫化铜锰蛋白复合纳米颗粒水溶液(PDAMn-CuS@BSA-FA，C CuS＝2.4mg mL-1)。以CuS为0.1mg mL-1配制PDAMn-CuS@BSA-FA复合纳米颗粒水溶液测紫外吸收图谱，得到CuS(800-1000nm)与有机荧光配体PDA(499nm)吸收峰的吸光度比为1：1.5(图1)。通过TEM电镜图显示纳米颗粒分散均一，有明显的蛋白包裹作用(图2)。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了44.7℃。
实施例2
以制备的硫化铜水溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)为模板，在72mL深绿色的柠檬酸盐包裹的硫化铜纳米晶体水溶液中加入600μL氯化锰(MnCl2·4H2O，248mM)溶液，混合均匀后放置在平台搅拌器上，室温搅拌10min(溶液中可见析出的深绿色颗粒)；将溶液转移到水浴中，缓慢滴加300μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)，有机荧光配体与Mn2+配位，升温至70℃，继续加热反应30min，形成稳定的配合物包裹的CuS纳米颗粒；反应结束后，缓慢降温至室温，降温时间为15min；将溶液转移至平台搅拌器上，逐滴滴加888μL BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，即可得到稳定的蛋白包裹的核壳结构的硫化铜锰蛋白复合纳米颗粒(PDAMn-CuS@BSA-FA)；后加入丙酮使纳米颗粒沉降，静置10h，将纳米颗粒重新分散在3mL去离子水中。以CuS浓度为0.1mg mL-1配制PDAMn-CuS@BSA-FA复合纳米颗粒水溶液测紫外吸收图谱，得到CuS与有机荧光配体PDA的吸光度比为1：1.7。通过TEM电镜图显示该比例制备的纳米颗粒较为团聚。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了32.7℃。
实施例3
以制备的硫化铜水溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)为模板，在72mL深绿色的柠檬酸盐包裹的硫化铜纳米晶体水溶液中加入300μL氯化锰(MnCl2·4H2O，248mM)溶液，混合均匀后放置在平台搅拌器上，室温搅拌10min(溶液中可见析出的深绿色颗粒)；将溶液转移到水浴中，缓慢滴加300μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)，配体与Mn2+配位，升温至70℃，继续加热反应30min，形成稳定的配合物包裹的CuS纳米颗粒；反应结束后，缓慢降温至室温，降温时间为15min；将溶液转移至平台搅拌器上，逐滴滴加1.5mL BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，即可得到稳定的蛋白包裹的核壳结构的硫化铜锰蛋白复合纳米颗粒(PDAMn-CuS@BSA-FA)；后加入丙酮使纳米颗粒沉降，静置10h，将纳米颗粒重新分散在3mL去离子水中。以CuS为0.1mg mL-1配制PDAMn-CuS@BSA-FA复合纳米颗粒水溶液测紫外吸收图谱，得到CuS与荧光配体PDA的吸光度比为1：0.2，几乎没有荧光配体的紫外吸收，说明过量蛋白BSA-PEG-FA表面吸附了大量的荧光配体，而未形成稳定的纳米复合颗粒。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了18.3℃。
实施例4
分步制备PDAMn-CuS@BSA-FA纳米复合物。
将0.8mL的MnCl2·4H2O(248mM)水溶液加入200mL制备好的CuS纳米晶体溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)中，放置2h，将析出颗粒离心，水洗涤，冷冻干燥备用，得到固体纳米颗粒CuS-Mn。称取1.2mg CuS-Mn分散于3mL乙醇中，移取100μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)逐滴加入其中，水浴回流，70℃，4h，反应结束后，离心，乙醇洗涤1次，乙腈洗涤1次，再乙醇洗涤一次，最后将固体分散在3mL乙醇中，配制PDAMn-CuS乙醇溶液(C CuS-Mn＝0.267mg/mL)，测紫外吸收光谱，得到CuS与荧光配体PDA的吸光度比为1：3，逐滴滴加0.5mL生物大分子蛋白BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，得到蛋白包裹的核壳结构的CuS纳米颗粒；后加入丙酮使纳米颗粒沉降，静静置10h，将纳米颗粒重新分散在3mL去离子水中。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为CCuS＝400μg mL-1)的温度在600s内增加了19.9℃。
实施例5
将0.8mL的MnCl2·4H2O(248mM)水溶液加入200mL制备好的CuS纳米晶体溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)中，放置2h，将析出颗粒离心，水洗涤，冷冻干燥备用，得到固体纳米颗粒CuS-Mn。称取2.4mg CuS-Mn分散于3mL乙醇中，移取100μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)逐滴加入其中，水浴回流，70℃，4h，反应结束后，离心，乙醇洗涤1次，乙腈洗涤1次，再乙醇洗涤一次，最后将固体分散在3mL乙醇中，配制PDAMn-CuS乙醇溶液(C CuS-Mn＝0.267mg/mL)，测紫外吸收光谱，得到CuS与荧光配体PDA的吸光度比为1：1.5，逐滴滴加0.8mL生物大分子蛋白BSA-PEG-FA(C BSA＝3.85mgmL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，得到蛋白包裹的核壳结构的硫化铜锰蛋白复合纳米颗粒；后加入丙酮使纳米颗粒沉降，静静置10h，将纳米颗粒重新分散在3mL去离子水中。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了25.4℃。
实施例6
将0.8mL的MnCl2·4H2O(248mM)水溶液加入200mL制备好的CuS纳米晶体溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)中，放置2h，将析出颗粒离心，水洗涤，冷冻干燥备用，得到固体纳米颗粒CuS-Mn。称取3.6mg CuS-Mn分散于3mL乙醇中，移取100μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)逐滴加入其中，水浴回流，70℃，4h，反应结束后，离心，乙醇洗涤1次，乙腈洗涤1次，再乙醇洗涤一次，最后将固体分散在3mL乙醇中，配制PDAMn-CuS乙醇溶液(C CuS-Mn＝0.267mg/mL)，测紫外吸收光谱，得到CuS与荧光配体PDA的吸光度比为1:1；逐滴滴加1mL BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌4h，得到蛋白包裹的核壳结构的硫化铜锰蛋白复合纳米颗粒；后加入丙酮使纳米颗粒沉降，静静置10h，重新分散在3mL去离子水中。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了16.1℃。
实施例7
将300μL氯化锰(MnCl2·4H2O，248mM)溶液和300μL有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液(8.4mM)混合，水浴加热，回流2h，70℃，得到PDAMn配合物。将PDAMn配合物溶液逐滴滴加至72mL深绿色的柠檬酸盐包裹的硫化铜纳米晶体水溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)中，室温平台搅拌器搅拌2h，升温至60℃反应2h，反应结束后，离心，洗涤，将固体重新分散于4mL蒸馏水中，逐滴滴加888μL BSA-PEG-FA(CBSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒，室温搅拌6h，得到蛋白包裹的核壳结构的硫化铜锰蛋白复合纳米颗粒；后加入丙酮使纳米颗粒沉降，静置10h，将纳米颗粒重新分散在3mL去离子水中。以CuS为0.1mg mL-1配制PDAMn-CuS@BSA-FA复合纳米颗粒水溶液测紫外吸收图谱，得到CuS与荧光配体PDA的吸光度比为1：0.8。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了34.4℃。
实施例8
分别移取0.5mL的有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)(8.4mM，4.2μmol)乙腈溶液和17μL MnCl2·4H2O水溶液(248mM，4.2μmol)，将两者混合于50mL的圆底烧瓶中，水浴加热回流2h，70℃，得到PDAMn配合物。移取12.6mL深绿色的柠檬酸盐包裹的硫化铜纳米晶体水溶液(硫化铜纳米晶体水溶液的浓度为0.1mg mL-1)，将反应后的PDAMn溶液逐滴滴加至上述溶液中，制备PDAMn-CuS纳米复合物，有深绿色固体析出，室温搅拌1h，升温至60℃继续反应1h，反应结束后，离心得固体，将固体重新分散于4mL乙醇中。在反应后的溶液中逐滴滴加888μL BSA-PEG-FA(C BSA＝3.85mg mL-1)水溶液控制形成均一纳米颗粒(PDAMn-CuS@BSA-FA)，室温下搅拌4h，反应结束后，将溶液离心，洗涤，重新分散在水溶液中。以CuS为0.1mg mL-1配制PDAMn-CuS@BSA-FA复合纳米颗粒水溶液测紫外吸收图谱，得到CuS与荧光配体PDA的吸光度比为1：1.8。用近红外激发光(808nm，2W/cm2)测试光热效应，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了39.8℃。
结合上述8种实施案例，得到了最佳合成比例的制备方法(实施例1)，该方法得到的PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的紫外光谱中出现明显的有机配体PDA(499nm)和CuS(800-1000nm)的特征吸收峰；从透射电镜图看出纳米颗粒尺寸均一，有明显的蛋白包裹的核壳结构；且在近红外激发光(808nm，功率为2W/cm2)的照射下，10min内PDAMn-CuS@BSA-FA复合纳米颗粒水溶液(浓度为C CuS＝400μg mL-1)的温度在600s内增加了44.7℃。实施例2是在实施例1的基础上增加二价锰离子的量，发现得到的纳米颗粒较为团聚。实施例3是在实施例1的基础上增加生物大分子蛋白BSA-PEG-FA的量，从得到的纳米颗粒的紫外光谱图中发现大部分有机荧光配体粘附在生物大分子蛋白上，从而未形成稳定的纳米复合颗粒。实施例4，5和6是分步法制备PDAMn-CuS@BSA-FA复合纳米颗粒，先制备CuS-Mn纳米颗粒，在不同量的CuS-Mn中加入有机荧光配体PDA进行组装，最后加入不同量的生物大分子蛋白BSA-PEG-FA进行包裹形成稳定的纳米颗粒，这三种实施案例测得的光热效率都较实施例1低。实施例7和8是先形成稳定的配合物PDAMn溶液，滴加到不同量的CuS纳米晶体溶液中，再加入生物大分子蛋白BSA-PEG-FA包裹形成稳定的纳米颗粒，得到的PDAMn-CuS@BSA-FA复合纳米颗粒光热效应比实施例1低。故实施例1是最佳合成案例，可得到较高转换效率的PDAMn-CuS@BSA-FA复合纳米颗粒水溶液。
PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的光热效应测试：
步骤一：取合成好的PDAMn-CuS@BSA-FA复合纳米颗粒水溶液，分别配制成3mL的25，50，100，200，400μg mL-1的PDAMn-CuS@BSA-FA复合纳米颗粒的水溶液；
步骤二：使用半导体激光光源(808nm，2W/cm2)分别照射不同浓度的PDAMn-CuS@BSA-FA复合纳米颗粒的水溶液，记录10min内温度变化。
步骤三：测量结果见附图。
Claims (10)
1.一种光热效应用硫化铜锰蛋白复合纳米颗粒，简称为PDAMn-CuS@BSA-FA复合纳米颗粒，其特征在于：将PDAMn-CuS@BSA-FA复合纳米颗粒分散在去离子水中，得到PDAMn-CuS@BSA-FA复合纳米颗粒的水溶液，在测试光热效应时，得到在近红外光照射下，PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的温度在10min内增加了44.7℃(空白：水的温度变化ΔT＝8.8℃)。
2.如权利要求1所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒，其特征在于：所述近红外光的波长为808nm，激发光源功率为2W/cm2；所述PDAMn-CuS@BSA-FA复合纳米颗粒水溶液的浓度为400μg mL-1。
3.如权利要求1所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒，其特征在于：所述PDAMn-CuS@BSA-FA复合纳米颗粒的粒径大小为20nm，其紫外-可见光区的特征吸收分别在499nm(PDA特征吸收)和900-1000nm(CuS特征吸收)处。
4.如权利要求1所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：以纳米硫化铜为模板，在深绿色的柠檬酸盐包裹的硫化铜纳米晶体溶液中加入氯化锰(MnCl2·4H2O)溶液，混合均匀后放置在平台搅拌器上，第一次室温搅拌后将溶液转移到水浴中，缓慢滴加有机荧光配体氟硼吡咯取代的二吡啶甲基胺(PDA)的乙腈溶液与Mn2+配位，20-70℃加热20-60min；缓慢降至室温；逐滴滴加生物大分子蛋白BSA-PEG-FA的水溶液控制形成均一纳米颗粒，转移到平台搅拌器上，第二次室温搅拌后加入丙酮使纳米颗粒沉降，静置8-12h后得到PDAMn-CuS@BSA-FA复合纳米颗粒。
5.如权利要求4所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：所述第一次室温搅拌的时间为5-15min；所述加热温度为70℃，加热时间为30min；所述降温时间为10-20min；所述第二次室温搅拌时间为3-5h；所述静置时间为10h。
6.如权利要求5所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：所述第一次室温搅拌的时间为10min；所述降温时间为15min；所述第二次室温搅拌时间为4h。
7.如权利要求4所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：所述的硫化铜纳米晶体水溶液的浓度为0.1mg mL-1，MnCl2·4H2O溶液的浓度为248mM，每1mL柠檬酸盐包裹的硫化铜纳米颗粒表面有2.04μmol羧基(CuS-COO-)；CuS-COO-与Mn2+的摩尔比为3:1-2:3。
8.如权利要求7所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：CuS-COO-与Mn2+的摩尔比为2:1。
9.如权利要求4所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：所述的氟硼吡咯取代的二吡啶甲基胺(PDA)与Mn2+的摩尔比为1:1-1:30；所述的BSA-PEG-FA与Mn2+的摩尔比为1:1000-1:2000。
10.如权利要求9所述的一种光热效应用硫化铜锰蛋白复合纳米颗粒的制备方法，其特征在于：所述的氟硼吡咯取代的二吡啶甲基胺(PDA)与Mn2+的摩尔比为1:29.52；所述的BSA-PEG-FA与Mn2+的摩尔比为1:1653。
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