CN115120748B - 一种靶向肿瘤的光声多模成像和光热治疗的纳米金属有机框架分子探针及其制备方法 - Google Patents
一种靶向肿瘤的光声多模成像和光热治疗的纳米金属有机框架分子探针及其制备方法 Download PDFInfo
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Abstract
本发明涉及生物医药技术领域，具体公开了一种用于主动靶向肿瘤的光声、MRI显像和光热、热消融治疗增敏的纳米金属有机框架(nMOF)分子探针及其制备方法。该所述分子探针具有核壳结构，以多模磁共振(MRI)造影剂功能与热消融增敏剂的普鲁士蓝铁基nMOF颗粒为核，吸附近红外二区荧光染料IR‑1061，外层包裹二氧化硅。本发明制备的(PB@IR1061@SiO2分子探针，缩写PIS)，具有近红外二区的吸收波长，生物相容、稳定性良好，能主动靶向肿瘤并富集。用近红外二区波长红外线(NIR II)等电磁波对靶组织辐照，该分子探针具有可视化靶向增强肿瘤光声、MRI多模成像；精准提高光热治疗，热消融增敏作用。
Description
技术领域
本发明涉及生物医药技术领域，尤其是涉及一种用于靶向肿瘤的光声、MRI显像和光热治疗、热消融(微波、射频、HIFU)增敏功能的纳米金属有机框架(nMOF)分子探针及其制备方法。
背景技术
近年来，作为一种非入侵式和非电离式的新型生物医学成像，光声成像技术迅速发展，其结合了组织显像中经典光学高选择性和传统超声深穿透性，具备高分辨率和高对比度的优点[1]。
热疗是一种利用高温来杀伤肿瘤的治疗方法，其中电磁波热和光热、聚焦超声能量是常用的三种热疗方式，即分别利用材料的磁热和光热、声热转换性能，有效地将磁和光能转换、聚焦声学能量为热能，产生高温杀伤肿瘤细胞。热疗可特异性的杀伤肿瘤细胞而对正常细胞影响微小，因此被医学界称之为“绿色疗法”。具有较高组织穿透能力的近红外光被广泛的应用于热疗中，通过将近红外光的能量辐照到肿瘤区域，使肿瘤区域升温达到43℃从而治疗肿瘤。而传统药物吲哚菁绿(ICG)等近红外染料是在近红外光照射下达到热疗效果[2]。
微波治疗通过照射，辐照区域极性分子间高速振荡，改变存在的磁阻阻尼机理产热；射频电流流经人体组织时，因电磁场的快速变化使得细胞内的正负离子快速运动，使得它们之间以及它们与细胞内的其它分子、离子等摩擦产热；HIFU(即聚焦超声)，通过聚集声能机理产热。微波、射频、HIFU等不同波谱电磁波使靶肿瘤组织快速升温、在肿瘤部位诱导细胞凋亡、甚至直接凝固坏死。
普鲁士蓝铁基nMOF(Prussian Blue，PB)是经典光声成像的造影剂，具有多孔结构、大的比表面积、多样化的形态和良好的生物降解性，是微波、射频、HIFU热消融治疗增敏剂[3]。普鲁士蓝作为一种铁基金属有机框架(Fe-MOF),不仅是经典光声成像的造影剂，还用作磁共振(MRI)造影(增强)剂[4]。
另外，普鲁士蓝铁基MOF具有过氧化氢酶功能，催化肿瘤内部的H2O2产生氧气，改善肿瘤乏氧环境，通过缓解对肿瘤化疗的耐药性，而发挥治疗功能[5,6]。
纳米医学的发展，为治疗药物、影像诊断显影剂的高效递送提供了契机，包括高分子及无机物材料的纳米载体，广泛应用于各种药物的输送。最近发现对纳米载体进行靶向分子的修饰(例如：抗体)，可以提高纳米载体的肿瘤靶向性；但是脱靶效应导致靶向效率低与存在一定生物毒性，影响纳米载体技术的发展。随着细胞生物膜(如红细胞膜，白细胞膜，癌细胞膜)等技术的兴起，越来越多的研究证明：通过纳米载体上包裹细胞生物膜，提高纳米药物体内血液循环时间，增强生物相容性，降低荷载药物的泄露，大大提高纳米载体的递送效率[7,8]。
主要选用小分子染料、二维材料、贵金属材料、碳基材料和纳米复合物等材料制备制备的外源性纳米探针，在实体肿瘤具有被高渗透滞留(EPR)效应，被动靶向到肿瘤病灶区，或通过在纳米颗粒上连接特异靶向分子，主动靶向到肿瘤区域。探针的主被动靶向性能提高光声成像的灵敏度和光热治疗的特异性。但是这些探针材料通常水溶性欠佳，荷载与包裹小分子药物(染料)在体内输送时容易泄漏；同时外源性探针易被机体多个防御机制清除，在体内血液循环存留时间短，对肿瘤靶向特异性差。纳米探针借助各种修饰、偶联、免疫细胞吞噬、细胞膜包裹等手段对其进行表面改性，以增强其靶向性、水溶解性和稳定性等特性。
为了实现可视化肿瘤的无创多模显像以及精准靶向治疗，在包含近红外线二区等波谱段红外线等电磁波辐照，以巨噬细胞吞噬专门制备探针后主动靶向肿瘤，开发红外光谱(及多种电磁波)下的光声诊断分子显影与光热治疗，兼有MRI显影(造影)剂、热消融(微波、射频、HIFU)增敏剂的纳米新型生物医药探针具有重要意义。
发明内容
本发明的目的：克服上述现有技术的不足，提供一种纳米金属有机框架(nMOF)分子探针及其制备方法。它具有核壳结构，以有多模磁共振(MRI)造影显影剂功能与热消融增敏剂基质的材料---即普鲁士蓝铁基nMOF颗粒为核，吸附近红外二区荧光染料IR-1061，在二者的外层包裹二氧化硅，制成光声、光热为核芯的多功能分子探针。本发明制备用于靶向肿瘤的光声及多模成像和肿瘤光热、增强热消融(微波、射频、HIFU)治疗的纳米金属有机框架(nMOF)分子探针(PIS)。特点是具有近红外二区的吸收波长。探针为巨噬细胞吞噬后，主动靶向肿瘤，并在肿瘤部位富集。利用具有良好的组织穿透性的近红外二区波长红外线(NIR II)(等电磁波)对肿瘤组织进行辐照，该分子探针具有可视化靶向增强肿瘤光声显影、MRI多模显像效能；精准提高对肿瘤光热治疗的功效，有热消融(微波、射频、HIFU)增敏剂作用。
近红外二区(NIR II)波长对组织具有良好的穿透性，可以增强光声成像和光热治疗的特异性与有效性。
为实现上述目的，本发明采取的技术方案为：
第一目的，本发明提供了一种可视化主要用于靶向肿瘤的光声成像和光热治疗的纳米金属有机框架(nMOF)分子探针(PIS)，所述纳米金属有机框架(nMOF)分子探针(PIS)具有核壳结构，以普鲁士蓝纳米颗粒为核，近红外二区荧光染料IR-1061吸附于普鲁士蓝纳米颗粒的表面为壳，在核壳结构的外层包裹二氧化硅形成分子探针(PIS)；
所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为(1-5):(1-5)。
本发明首先采用物理吸附法，使近红外二区荧光染料IR1061小分子吸附于普鲁士蓝纳米颗粒的表面；用溶胶-凝胶法，在核壳结构的外层包裹一层二氧化硅壳，这样不仅降低近红外二区荧光染料IR1061的泄漏，而且提高分子探针的稳定性和生物相容性。同时，利用巨噬细胞作为生物体内的免疫细胞，对肿瘤具有天然的靶向特异性特点。当巨噬细胞吞噬该分子探针后，将分子探针靶向输送到肿瘤部位，增加在肿瘤区域的富聚，从而提高光声成像的灵敏度和光热治疗效果。
本发明选用二氧化硅包裹核壳结构的外层，防止近红外二区荧光染料IR1061从普鲁士蓝纳米颗粒的表面脱落，血液递送中泄漏，增加了分子探针的稳定性。
作为本发明所述用于主动靶向肿瘤的光声成像和光热治疗的纳米金属有机框架(nMOF)分子探针的优选实施方式，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为1:(0.5-1.1)。
当普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061选用上述质量比时，该染料IR-1061更为稳定的吸附于普鲁士蓝纳米颗粒的表面，避免IR-1061在体内输送时泄漏。
第二目的，本发明以普鲁士蓝铁基纳米金属有机框架纳米(Fe-nMOF)颗粒为核，Fe-nMOF颗粒同时具备磁共振(MRI)多模造影剂作用；用于近红外二区波长红外线光声领域显影与光热治疗，功效高而不限制于此，在微波与射频、HIFU领域，为热消融增敏剂基质，有多谱波段电磁波热消融(RF、MW、HIFU)治疗增敏(效)作用。
普鲁士蓝吸附近红外二区荧光染料IR-1061，在二者的外层包裹二氧化硅形成分子探针。本发明制备PIS(PB@IR1061@SiO2缩写)分子探针具有近红外二区的吸收波长，具有较佳的稳定性和生物相容性。探针为巨噬细胞吞噬后，主动靶向肿瘤，并在肿瘤部位的富集。利用具有良好的穿透性近红外二区波长红外线(NIR II)等电磁波对组织辐照，该分子探针具有可视化靶向增强肿瘤光声显影、MRI多模分子显像；精准提高光热治疗功效，有热消融(微波、射频、HIFU)增敏剂作用。
第三目的，本发明还提供一种用于靶向肿瘤的光声、MRI成像和光热治疗、热消融增敏的纳米金属有机框架(nMOF)分子探针(PIS)的制备方法，包括以下步骤：
S1、称取普鲁士蓝纳米颗粒、近红外二区荧光染料IR-1061分别溶于去离子水和溶剂中，借助超声搅拌混合均匀，形成普鲁士蓝-IR1061混合溶液；
S2、称取十六烷基三甲基溴化铵、去离子水和无水乙醇形成混合液A，将普鲁士蓝-IR1061混合溶液加入至混合液A中混合，形成混合液B；
S3、在混合液B中加入正硅酸四乙酯搅拌混匀，制得用于靶向肿瘤的光声、MRI显像和光热治疗、热消融增敏的纳米金属有机框架分子探针。
作为本发明所述制备方法的优选实施方式，所述溶剂包括二甲基亚砜、二氯甲烷、丙酮、MeOH和二甲基甲酰胺中的任意一种。
本发明选用二甲基亚砜作为溶解近红外二区荧光染料IR-1061的溶剂，使得近红外二区荧光染料IR-1061小分子更易于被溶解。
作为本发明所述制备方法的优选实施方式，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为(1-5):(1-5)。
作为本发明所述制备方法的优选实施方式，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为1:(0.5-1.1)。
作为本发明所述制备方法的优选实施方式，所述近红外二区荧光染料IR-1061和十六烷基三甲基溴化铵的质量比为(1-5mg):(0.1g-0.3g)。
本发明还提供上述分子探针在制备可视化靶向增强肿瘤光声成像显影、MRI多模成像造影剂、光热治疗制剂和热消融增敏剂中的应用。
作为本发明所述应用的优选实施方式，所述分子探针的浓度为1-200μg/mL。
与现有技术相比，本发明具有以下有益效果：
本发明提供了一种可视化靶向肿瘤的光声、MRI显像和光热治疗、热消融增敏的纳米金属有机框架(nMOF)分子探针PIS及其制备方法，本发明通过把近红外二区荧光染料IR1061小分子，吸附于普鲁士蓝纳米颗粒的表面，然后在核壳结构的外层包裹一层二氧化硅壳，制备得到的分子探针PIS稳定性和生物相容性良好，上述核层结构可以防止近红外二区荧光染料IR1061的泄漏，本发明的纳米金属有机框架(nMOF)分子探针血液循环时间较长，而提高递送有效性；为巨噬细胞吞噬后，主动靶向肿瘤，并在肿瘤部位的富集；增强该分子探针对肿瘤光声显像的靶向精准性和光热治疗的有效性。
附图说明
图1为PIS纳米金属有机框架(nMOF)探针的合成示意图；
图2为PIS纳米金属有机框架(nMOF)探针的物理表征图(图2-a为PIS的透射电镜图；图2-b为PIS纳米颗粒的粒径分布图；图2-c为不同材料(PIS、PB@SiO2、IR1061)的吸收光谱图；图2-d为不同材料(PIS、PB@SiO2、IR1061)的zeta电位图)；
图3为巨噬细胞吞噬PIS纳米金属有机框架(nMOF)探针的验证图(右下标为50μm)；
图4为PIS纳米金属有机框架(nMOF)探针的光声性能表征图；
图5为PIS纳米金属有机框架(nMOF)探针的光热性能表征图；
图6为PIS纳米金属有机框架(nMOF)探针的细胞毒性和光热毒性表征图；
图7为PIS纳米金属有机框架(nMOF)探针的溶血实验结果图；
图8为有机小分子染料IR1061在不同有机溶剂中的紫外-可见吸收光谱；
图9为有机小分子染料IR1061在不同有机溶剂中合成PIS的紫外-可见吸收光谱；
图10为普鲁士蓝纳米颗粒分别与不同比例的有机小分子染料IR1061进行探针合成后的紫外-可见吸收光谱；
图11为PIS在Balb/c小鼠荷瘤光声成像图；
图12为PIS在Balb/c小鼠荷瘤光热显像图；
图13为生理盐水(对照组)和普鲁士蓝纳米颗粒(实验组)T1加权MRI显示图像。
具体实施方式
为更好的说明本发明的目的、技术方案和优点，下面将结合附图和具体实施例对本发明作进一步说明。
在以下实施例中，所使用的实验方法如无特殊说明，均为常规方法，所用的材料、试剂等，如无特殊说明，均可从商业途径得到。
实施例1、PIS纳米金属有机框架(nMOF)探针及其制备方法
该实施例提供PIS纳米金属有机框架(nMOF)探针的制备方法，包括以下步骤：
分别称取1-5mg的普鲁士蓝纳米颗粒和1-5mg的近红外二区荧光染料IR-1061(最佳比例为1:1，例如1mg：1mg)分别溶于水和二甲基亚砜(DMSO)中，超声混匀10min，使二者充分溶解，形成普鲁士蓝-IR1061混合溶液；然后称取0.1g-0.3g十六烷基三甲基溴化铵(CTAB)，去离子水1-2ml，无水乙醇15-18ml，充分混匀，形成混合液A；将普鲁士蓝-IR1061混合溶液加入到混合液A中，35℃，磁力搅拌1h，形成混合液B；然后在混合液B加入100-300μl的正硅酸四乙酯(TEOS)，继续搅拌1h。反应完成后，高速离心，用去离子水洗涤2-3次；制得用于靶向肿瘤的光声、MRI成像和光热治疗、热消融增敏的分子探针(PIS纳米金属有机框架(nMOF)探针，合成示意图如图1所示)，然后将制得的分子探针与巨噬细胞共孵育2-4h。
上述制备的PIS纳米金属有机框架(nMOF)探针的物理表征如图2所示；图2-a为PIS的透射电镜图，结果显示该纳米颗粒为球状均匀颗粒；图2-b为PIS探针纳米颗粒的粒径分布图，结果显示该纳米颗粒的平均粒径为90nm；图2-c为不同材料(PIS、PB@SiO2、IR1061)的吸收光谱图，结果显示IR1061小分子被成功包裹于普鲁士蓝中，PIS在二区红外线吸收光谱良好。图2-d为不同材(PIS、PB@SiO2、IR1061)的zeta电位图，结果显示PIS纳米颗粒的平均zeta电位为30mV。
如图3所示，PIS纳米金属有机框架(nMOF)探针被巨噬细胞吞噬到胞内，证实明巨噬细胞可以作为该纳米颗粒的载体。
如图4所示，不同浓度(50-200μg/mL)PIS纳米金属有机框架(nMOF)探针的光声信号值，显示光声信号强度与纳米颗粒的浓度呈线性关系。
如图5所示，PIS纳米金属有机框架(nMOF)探针具有良好的光热效果，光热效果随着浓度(1-20ug/mL)的升高而增强。
上述制备的PIS纳米金属有机框架(nMOF)探针的细胞毒性和光热毒性表征如图6所示；图6-a为不同浓度的普鲁士蓝溶液对4T1细胞的毒性试验结果，显示普鲁士蓝细胞毒性低。图6-b为不同浓度的PIS对RAW264.7和4T1细胞的毒性结果，同样显示SPB纳米颗粒细胞毒性低。图6-c和图6-d为纳米颗粒的光热毒性结果，可以看出在近红外光照射后，PIS@M(M表示巨噬细胞，PIS@M指代吞噬探针后的巨噬细胞)能够杀死4T1乳腺癌细胞，证明该纳米颗粒具有良好的光热治疗效果。
如图7所示，PIS纳米金属有机框架(nMOF)探针与红细胞悬液混合后，血液红细胞溶血率低，证明该PIS纳米金属有机框架(nMOF)探针具有良好的生物相容性。
参考图8为有机小分子染料IR1061在不同有机溶剂(二甲基亚砜、二氯甲烷、丙酮、MeOH或二甲基甲酰胺)中的紫外-可见吸收光谱。
参考图9，有机小分子染料IR1061在不同有机溶剂中合成PIS的紫外-可见吸收光谱。如图可见，当DMSO作为IR1061溶剂时，在700nm左右(普鲁士蓝吸收峰)和1061nm(IR1061吸收峰)均有良好的吸收。因此选择DMSO作为IR1061的反应溶剂。
参考图10，不同比例的有机小分子染料IR1061，分别与普鲁士蓝纳米颗粒进行合成探针后的紫外-可见吸收光谱。如图10可见，当有机小分子染料IR1061与普鲁士蓝纳米颗粒质量比为1:1时，PIS具有良好的吸收峰。因此普鲁士蓝与IR1061的最佳质量比为1:1。
参考图11，该图为PIS在Balb/c小鼠荷瘤光声显像图。可见PIS在激光照射下具有良好的光热能力，能够达到消灭肿瘤的温度。
参考图12，该图为PIS在Balb/c小鼠荷瘤光热显像图。显示：PIS随着时间的延长，随巨噬细胞逐渐在肿瘤部位富集，并在9h显示到达最高峰。
参考图13，该图为体外普鲁士蓝T1核磁共振成像。图a为实物图，图b左右两个样品分别为0.9％的生理盐水(对照组)和普鲁士蓝溶液(实验组)。由图显示普鲁士蓝具有良好的T1加权MRI信号。
缩写与注释：
1.纳米金属有机框架(nano Metal Organic Fragment，nMOF)。
2.PB@IR1061@SiO2纳米金属有机框架(nMOF)探针，在本文等同该纳米颗粒(分子探针)。
3.PIS为PB@IR1061@SiO2缩写。PB为Prussian Blue缩写。
4.PIS@M(M表示巨噬细胞，PIS@M指代吞噬探针后的巨噬细胞)。
5.PB@IR1061@SiO2纳米金属有机框架是全新化学生物医药材料，在不同亚学科与用途用作不同专业术语名称，本说明书该纳米金属有机框架在光学、光声、超声叫探针(probe)。如photoacoustic probe Sonication probe超声探针。
6.PB@IR1061@SiO2在微波、射频、聚焦超声领域术语增敏剂(synergist)，Radiofrequency(RF)synergist、Microwave(MW)synergist。
7.PB@IR1061@SiO2在光声、超声、radiology、磁共振等影像术语叫造影剂(Imagecontrast agents)。
参考文献：
[1]MANOHAR S,DANTUMA M.Current and future trends in photoacousticbreast imaging[J].Photoacoustics,2019,16(100134.
[2]LEE D E,KOO H,SUN I C,et al.Multifunctional nanoparticles formultimodal imaging and theragnosis[J].Chem Soc Rev,2012,41(7):2656-72
[3]PAULIDES M M,DOBSICEK TREFNA H,CURTO S,et al.Recent technologicaladvancements in radiofrequency-andmicrowave-mediated hyperthermia forenhancing drug delivery[J].Adv Drug Deliv Rev,2020,163-164(3-18.
[4]QIN Z,CHEN B,MAO Y,et al.Achieving Ultrasmall Prussian BlueNanoparticles as High-Performance Biomedical Agents with Multifunctions[J].ACS Appl Mater Interfaces,2020,12(51):57382-90.
[5]ZHANG W,HU S,YIN J J,et al.Prussian Blue Nanoparticles asMultienzyme Mimetics and Reactive Oxygen Species Scavengers[J].J Am Chem Soc,2016,138(18):5860-5..
[6]LI H,WANG M,HUANG B,et al.Theranostic near-infrared-IIb emittingnanoprobes for promoting immunogenic radiotherapy and abscopal effectsagainst cancer metastasis[J].Nat Commun,2021,12(1):7149.
[7]OROOJALIAN F,BEYGI M,BARADARAN B,et al.Immune Cell Membrane-CoatedBiomimetic Nanoparticles for Targeted Cancer Therapy[J].Small,2021,17(12):e2006484.
[8]CHEN L,ZHOU L,WANG C,et al.Tumor-Targeted Drug and CpG DeliverySystem for Phototherapy and Docetaxel-Enhanced Immunotherapy withPolarization toward M1-Type Macrophages on Triple Negative Breast Cancers[J].Adv Mater,2019,31(52):e1904997.
最后所应当说明的是，以上实施例仅用以说明本发明的技术方案而非对本发明保护范围的限制，尽管参照较佳实施例对本发明作了详细说明，本领域的普通技术人员应当理解，可以对本发明的技术方案进行修改或者等同替换，而不脱离本发明技术方案的实质和范围。
Claims (10)
1.一种用于靶向肿瘤的光声、MRI显像和光热治疗、热消融增敏效能的纳米金属有机框架分子探针，其特征在于，所述纳米金属有机框架分子探针具有核壳结构，以普鲁士蓝纳米颗粒为核，近红外二区荧光染料IR-1061吸附于普鲁士蓝纳米颗粒的表面为壳，在核壳结构的外层包裹二氧化硅形成分子探针。
2.如权利要求1所述的纳米金属有机框架分子探针，其特征在于，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为(1-5):(1-5)。
3.如权利要求2所述的纳米金属有机框架分子探针，其特征在于，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为1:(0.5-1.1)。
4.一种用于靶向肿瘤的光声、MRI显像和光热治疗、热消融增敏的纳米金属有机框架分子探针的制备方法，其特征在于，包括以下步骤：
S1、称取普鲁士蓝纳米颗粒、近红外二区荧光染料IR-1061分别溶于去离子水和溶剂中，超声混匀，形成普鲁士蓝-IR1061混合溶液；
S2、称取十六烷基三甲基溴化铵、去离子水和无水乙醇形成混合液A，将普鲁士蓝-IR1061混合溶液加入至混合液A中混合，形成混合液B；
S3、在混合液B中加入正硅酸四乙酯搅拌混匀，制得用于靶向肿瘤的光声、MRI显像和光热治疗、热消融增敏的纳米金属有机框架分子探针。
5.如权利要求4所述的制备方法，其特征在于，所述溶剂包括二甲基亚砜、二氯甲烷、丙酮、MeOH和二甲基甲酰胺中的任意一种。
6.如权利要求4所述的制备方法，其特征在于，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为(1-5):(1-5)。
7.如权利要求6所述的制备方法，其特征在于，所述普鲁士蓝纳米颗粒与近红外二区荧光染料IR-1061的质量比为1:(0.5-1.1)。
8.如权利要求4所述的制备方法，其特征在于，所述近红外二区荧光染料IR-1061和十六烷基三甲基溴化铵的质量比为(1-5mg):(0.1g-0.3g)。
9.如权利要求1-3任一项所述的纳米金属有机框架分子探针在制备可视化靶向增强肿瘤光声成像显影、MRI多模成像造影剂、光热治疗制剂和热消融增敏剂中的应用。
10.如权利要求9所述的应用，其特征在于，所述纳米金属有机框架分子探针的浓度为1-200μg/mL。
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