CN108939094A - 一种装载纳米颗粒的微纳气泡及其超声标记干细胞的方法与应用 - Google Patents
一种装载纳米颗粒的微纳气泡及其超声标记干细胞的方法与应用 Download PDFInfo
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Abstract
一种装载纳米颗粒的微纳气泡及其超声标记干细胞的方法与应用,属于纳米生物医学技术领域。所述装载纳米颗粒的微纳气泡包括气体内核和气泡膜壳,所述气体内核由生物医学用气体组成,所述气体膜壳为生物医学影像增强用纳米颗粒,所述气泡膜壳层层自组装于气体内核。所述装载纳米颗粒的微纳气泡能够结合超声能量调控实现气泡或气泡上携载的纳米颗粒无损高效率转载进入干细胞,实现生物医学影像用纳米颗粒长程示踪干细胞的标记方法和应用。可以结合超声、磁共振、计算机断层(CT)、光声等一种或多种联合的医学成像模态对干细胞进行在体成像和示踪,推动干细胞基础研究和临床应用研究的发展,实现干细胞精准体内治疗的有效和安全。
Description
技术领域
本发明属于纳米生物医学技术领域,具体涉及一种装载纳米颗粒的微纳气泡及其超声标记干细胞的方法与应用。
背景技术
干细胞具有分化成多种细胞及组织和调节局部免疫环境等功能,是当前神经损伤、肝衰竭等重大疾病治疗的变革性治疗手段的重要方向之一。然而,作为使用干细胞进行体内治疗的先决条件,我们需要准确示踪它们在体内病灶部位的归巢、迁移、分布、增殖及分化等生物学行为。当前主要通过最终的病理组织切片进行评价,无法实现准确、客观、实时动态的精准监测。因此,发展一种非损伤的干细胞示踪技术,以了解移植干细胞在活体内的分布、靶向以及功能分化,对有效干细胞疗法的开发及其临床转化都具有重大意义。包括光学成像、光声成像、磁共振(MRI)成像、核医学成像、计算机断层(CT)成像和超声(US)成像等模式在内的生物医学影像能够通过影像学信息的提取,表征干细胞的活性和分化等生物功能,已经成为干细胞移植及研究中必不可少的一部分。然而开发何种影像示踪剂以及采用哪种恰当的干细胞标记技术才能实现生物医学造影增强剂材料才能实现对干细胞无损、高效的标记仍存在技术瓶颈,尤其如何实现干细胞分裂过程中标记的造影增强剂不被影响,且能更长时间滞留在干细胞内而不干扰干细胞的正常生物学功能成为研究热点和技术难点。
当前医学造影剂使用的纳米颗粒包括磁性纳米颗粒、微纳气泡、贵金属纳米颗粒(金、银等纳米颗粒)、无机纳米颗粒、有机纳米颗粒、脂质体等,这些纳米材料主要通过共孵育后的内吞或吞噬机制进入细胞,但是孵育时间极长,在此基础上为了使细胞迅速有效的摄取纳米粒子,亦可通过合理的纳米颗粒表面修饰、纳米化学和纳米颗粒表面连接相关的生物分子等方式实现。然而,这种方法在纳米颗粒与细胞共孵育过程中仍然存在需要较长时间的纳米颗粒与干细胞的相互作用(超过10 h),可能会引起细胞膜破裂,细胞骨架紊乱,细胞毒性和对标记细胞的存活和增殖造成有害影响。因此,如若采用当前的技术和方法,对干细胞进行纳米造影剂的标记存在标记效率低、损伤干细胞形貌和功能等风险。
发明内容
解决的技术问题:针对现有技术中存在生物医学影像用纳米颗粒标记干细胞时标记数量少、存活率低、细胞内靶向定位不确定等问题,本发明提供一种装载纳米颗粒的微纳气泡及其超声标记干细胞的方法与应用,能够实现安全、稳定、可靠将纳米示踪剂标记到干细胞内,并结合超声、磁共振、计算机断层、光声等一种或几种生物医学成像技术对干细胞进行在体成像和示踪,推动干细胞基础研究和临床应用研究的发展,实现干细胞精准体内治疗的有效和安全。
技术方案:一种装载纳米颗粒的微纳气泡,所述装载纳米颗粒的微纳气泡包括气体内核和气泡膜壳,所述气体内核由生物医学用气体组成,所述气体膜壳为生物医学影像增强用纳米颗粒,所述气泡膜壳层层自组装于气体内核。
作为优选,所述生物医学用气体为惰性气体和生物活性气体中的至少一种,所述惰性气体为氮气、六氟化硫或全氟化碳,所述生物活性气体为一氧化氮、硫化氢或氧气。
作为优选,所述生物医学影像增强用纳米颗粒为磁共振成像增强剂用超顺磁性纳米颗粒、携载钆或磁性纳米颗粒的纳米囊或脂质体、CT成像增强剂金纳米颗粒和携载金纳米颗粒的纳米囊或脂质体中的至少一种。
作为优选,所述载纳米颗粒的微纳气泡的尺寸为100~1500 nm,浓度为5×107个/mL~5×108个/mL。
作为优选,所述生物医学用气体由溶气泵法制备,浓度为5.5×108~60×108个/mL。
作为优选,所述生物医学影像增强用纳米颗粒的粒径为5~100 nm,生物医学影像增强用纳米颗粒与生物医学用气体的浓度比值为(100 µg:1个)~(1 µg:100个)。
所述装载纳米颗粒的微纳气泡超声标记干细胞的方法,所述方法步骤如下:首先将装载纳米颗粒的微纳气泡与干细胞均匀混合,然后通过磁场或超声场进行物理场调控装载纳米颗粒的微纳气泡与干细胞相互作用和结合,实现微纳气泡或纳米气泡破裂释放纳米颗粒标记干细胞。
作为优选,所述超声场为超声波,所述超声波的发射选用平阵探头或聚焦探头,频率0.2~3 MHz,声强为0.05~2.5 MPa,超声作用时间0.25~30 min;所述磁场为静磁场,矫顽力为10~25 Oe,表面磁感应强度为10~1000 mT,磁场作用时间 20~40 min。
作为优选,所述干细胞为神经干细胞、间充质干细胞或者诱导性多能干细胞。
所述装载纳米颗粒的微纳气泡在制备标记干细胞、超声或磁场引导干细胞靶向病变组织、利用生物医学成像技术对干细胞进行在体成像和示踪试剂中的应用。
本发明所述干细胞标记示踪用的携载纳米颗粒的微纳气泡一般制备方法和超声介导纳米颗粒标记干细胞的一般操控方法如下:
(1)采用层层自组装技术构建包含一种或几种影像示踪剂的纳米颗粒材料作为微纳气泡膜壳材料,构成了具有超声单一模态成像或超声、磁共振、计算机断层(CT)、光声等多模态成像功能。如超顺磁性γ-三氧化二铁纳米颗粒与微纳气泡的组装体可实现磁共振/超声双模态成像;金纳米颗粒与微纳气泡的组装体可实现CT/超声双模态成像;超顺磁性γ-三氧化二铁纳米颗粒、金纳米颗粒与微纳气泡的组装体可实现磁共振/CT/超声三模态成像;
(2)将上述携载纳米颗粒与干细胞相互作用,首先通过显微、超声显影技术监测携载纳米颗粒的微纳气泡在干细胞表面的分布,然后通过调控超声辐照参数条件或磁场条件,控制吸附在干细胞表面的微纳气泡或气泡破泡后释放携载的纳米颗粒定向控制进入干细胞内,实现纳米颗粒无损、安全、靶向定位干细胞内。
有益效果:
本发明通过制备携载纳米颗粒的微纳气泡材料,利用微纳气泡对超声场的特异性响应和操控,实现携载纳米颗粒的微纳气泡破泡瞬时声穿孔效应,将气泡上装载的纳米颗粒释放出来后,无损、快速输送进入干细胞细胞质内,实现干细胞的纳米颗粒短时、高效率标记和长程影像学示踪监测,以保障干细胞体内应用的安全性和可靠性。
本发明所述干细胞标记示踪的携载纳米颗粒的微纳气泡具有短时(0.25~30min),标记干细胞的效率达96%,同时具有体内超声、磁场靶向导航以及超声、磁共振、CT、光声等多模态成像示踪的功能,为实现精准干细胞治疗提供了高时空分辨率的示踪材料和技术手段。
附图说明
图1为本发明所述装载纳米颗粒的微纳气泡组装体结构示意图。
图2为本发明实施例3中载金纳米颗粒的气泡标记神经干细胞6 h后,神经干细胞超声显影结果图,图中a为B超显影结果图,b为造影显影结果图。
图3为本发明实施例3中载金纳米颗粒的气泡标记神经干细胞12天后,神经干细胞干性巢蛋白表达显微结果图。
图4为本发明实施例4中载磁性纳米颗粒的气泡标记神经干细胞24 h后,普鲁士蓝染色显微结果图。
具体实施方式
下面结合附图和具体实施例对本发明作进一步描述,应理解这些实施方式仅用于说明本发明而不用于限制本发明的范围,在阅读本发明之后,本领域的技术人员对本发明的各种等价形式的修改均落于本申请的权利要求所限定的范围。
实施例1
参照图1,本发明所述装载纳米颗粒的微纳气泡包括气体内核和气泡膜核,所述气泡内核由生物医学用气体组成,所述气泡膜壳为生物医学影像增强用纳米颗粒,所述气泡膜壳层层自组装于气体内核。
本实施例中所述生物医学用气体为六氟化硫,所述生物医学影像增强用纳米颗粒为磁共振成像增强剂用超顺磁性四氧化三铁纳米颗粒,超顺磁性四氧化三铁纳米颗粒随机分布在气体内核表面。所述气泡膜壳层层自组装于气体内核的方法如下:组装前将超顺磁性四氧化三铁纳米颗粒表面采用生物相容性的聚丙烯酸进行修饰,然后通过气液泵装置将气液共混合(气液体积比为5:1)制备溶气水的方法,制备包含六氟化硫气体的自由气泡水溶液,然后将新鲜制备的六氟化硫溶气水迅速注满3 mL的试剂瓶,加入200 µg的超顺磁性四氧化三铁纳米颗粒,密封、静置8 h后,在800 rcf(相对离心力)离心30 min,取上清液,即得装载磁性纳米颗粒的六氟化硫微纳气泡水溶液。
制备的微纳气泡浓度为5×108个/mL,粒径为200 nm。得到的磁性微纳气泡具有超声成像能力,进而由于膜壳上磁性纳米颗粒的分布而具有磁共振成像能力,提供了双模态成像和失踪功能。
制备的装载磁性纳米颗粒的六氟化硫微纳气泡超声标记干细胞的方法如下:将制备的装载磁性纳米颗粒的六氟化硫微纳气泡与干细胞混合,干细胞的浓度为5×106个/mL,置于超声场中进行超声处理,超声波的发射选用聚焦探头,频率为0.2 MHz,声强为0.05MPa,作用时间为0.25 min。
实施例2
参照图1,本发明所述装载纳米颗粒的微纳气泡包括气体内核和气泡膜核,所述气泡内核由生物医学用气体组成,所述气泡膜壳为生物医学影像增强用纳米颗粒,所述气泡膜壳层层自组装于气体内核。
本实施例中所述生物医学用气体为六氟化硫,所述生物医学影像增强用纳米颗粒为金纳米颗粒,金纳米颗粒随机分布在气体内核表面。所述气泡膜壳层层自组装于气体内核的方法如下:通过气液混合制备溶气水的方法制备包含六氟化硫气体的自由气泡水溶液,然后将新鲜制备的六氟化硫溶气水迅速注满3 mL的试剂瓶,加入350 µg的金纳米颗粒,密封、静置8 h后,在800 rcf(相对离心力)离心30 min,取上清液,即得装载金纳米颗粒的六氟化硫微纳气泡水溶液。
制备的微纳气泡浓度为5×107个/mL,粒径为200 nm。得到的金纳米颗粒微纳气泡具有超声成像能力,进而由于膜壳上金纳米颗粒的分布而具有CT成像和光声成像能力,提供三模态成像和示踪功能。
制备的装载金纳米颗粒的六氟化硫微纳气泡超声标记干细胞的方法如下:将制备的装载金纳米颗粒的六氟化硫微纳气泡与干细胞混合,干细胞的浓度为5×106个/mL,置于超声场中进行超声处理,超声波的发射选用聚焦探头,频率为3 MHz,声强为2.5 MPa,作用时间为30 min。
实施例3
采用实施例2制备的装载金纳米颗粒的六氟化硫微纳气泡对海马神经干细胞进行超声标记。具体方法如下:
(1)海马神经干细胞(hNSC)的分离、纯化和鉴定
分离、纯化 选择孕14天SD大鼠,颈椎脱臼处死后于75 vt.%酒精浸泡消毒。无菌条件下取胎鼠脑组织,用PBS缓冲液浸泡脑组织,清除血管膜,取海马组织,反复冲洗(冰上操作)。用剪刀将海马组织剪碎,加入0.25 vt.% 胰蛋白酶2 mL于37℃水浴消化5 min,4 mLDMEM/F12-10 wt.%FBS终止消化后于1000 rpm离心5 min,弃上清液,用NSCs生长培养基(DMEM/F12+2 wt.% B27+20 ng/mL EGF+20 ng/mL bFGF)重悬细胞。400目细胞筛过滤上述重悬液并于1000 rpm离心5 min,再用NSCs生长培养基重悬细胞沉淀,吹打均匀后接种到细胞瓶中置于培养箱(37℃,5 vt.% CO2)培养标记为原代海马神经干细胞P0,之后每2-3天半量换液,待细胞长至约100~150 μm时(约7~8 d),可进行细胞传代。
(神经干细胞)的鉴定 第三代NSCs形成神经球时,将其滴于预铺有多聚赖氨酸包被的培养板上,37℃、5 vt.% CO2、95 vt.%饱和湿度培养箱孵育2 h,吸出培养液,0.01mol/LPBS冲洗3次;加4 wt.%多聚甲醛固定30 min,PBS冲洗3次;0.1 wt.% TritonX-100透化20min,PBS冲洗3次;5 vt.% BSA封闭20 min,加入鼠Nestin单克隆抗体(质量比为1:100),4℃冰箱过夜;PBS冲洗3次,加入FITC标记的山羊抗鼠IgG (质量比为1:1000),37℃避光反应30min,PBS冲洗3次;加入DAPI反应5~10 min,封片后在荧光显微镜下观察。
(2)超声能量操控金纳米气泡与海马神经干细胞的相互作用
利用上述装载有金纳米颗粒的微纳气泡材料与干细胞混合,置于超声场中进行超声处理,微纳气泡浓度为5×107个/mL,粒径分布为200 nm;干细胞的浓度为5×106个/mL;超声波的发射选用聚焦探头,频率为1 MHz,声强为1.82 KPa,作用时间为40 s。采用CCK8法测定干细胞活性;并采用暗场成像、ICP发射光谱仪、细胞切片、超声成像等方式表征不同时间段内,经过超声处理后的干细胞内金纳米颗粒(气泡)的存在及分布情况,载金纳米颗粒的气泡标记神经干细胞6 h后,神经干细胞超声显影结果图参见图2,显影结果图中出现亮斑。载金纳米颗粒的气泡标记神经干细胞12天后,神经干细胞干性巢蛋白表达显微结果图参见图3。结果表明,经此超声条件下干预的神经干细胞体外活力可维持在96%,12天内对神经干细胞形态、细胞抗原表达没有明显影响。
实施例4
采用实施例1制备的装载磁性纳米颗粒的六氟化硫微纳气泡对海马神经干细胞进行磁场标记。具体方法如下:
利用上述装载有磁性纳米颗粒的微纳气泡材料与干细胞混合,置于超声场中进行超声处理,微气泡浓度为5×108个/mL,粒径分布为200 nm;干细胞的浓度为5×107个/mL;静磁场直径10 mm,厚度2 mm,矫顽力12.5 Oe,表明磁感应强度100 mT。采用CCK8法测定干细胞活性;并采用普鲁士蓝染色、ICP发射光谱仪、细胞切片、磁共振成像等方式表征不同时间段内经过超声处理后的干细胞内磁性纳米颗粒(气泡)的存在及分布情况。载磁性纳米颗粒的气泡标记神经干细胞24h后,普鲁士蓝染色显微结果图参见图4。载磁性纳米颗粒的气泡标记神经干细胞12天后,神经干细胞活力可维持在96%,神经干细胞形态、细胞抗原表达没有明显影响。
Claims (10)
1.一种装载纳米颗粒的微纳气泡,其特征在于,所述装载纳米颗粒的微纳气泡包括气体内核和气泡膜壳,所述气体内核由生物医学用气体组成,所述气体膜壳为生物医学影像增强用纳米颗粒,所述气泡膜壳层层自组装于气体内核。
2.根据权利要求1所述的一种装载纳米颗粒的微纳气泡,其特征在于,所述生物医学用气体为惰性气体和生物活性气体中的至少一种,所述惰性气体为氮气、六氟化硫或全氟化碳,所述生物活性气体为一氧化氮、硫化氢或氧气。
3.根据权利要求1所述的一种装载纳米颗粒的微纳气泡,其特征在于,所述生物医学影像增强用纳米颗粒为磁共振成像增强剂用超顺磁性纳米颗粒、携载钆或磁性纳米颗粒的纳米囊或脂质体、CT成像增强剂金纳米颗粒和携载金纳米颗粒的纳米囊或脂质体中的至少一种。
4.根据权利要求1所述的一种装载纳米颗粒的微纳气泡,其特征在于,所述载纳米颗粒的微纳气泡的尺寸为100~1500 nm,浓度为5×107个/mL~5×108个/mL。
5.根据权利要求1所述的一种装载纳米颗粒的微纳气泡,其特征在于,所述生物医学用气体由溶气泵法制备,浓度为5.5×108个/mL~60×108个/mL。
6.根据权利要求1所述的一种装载纳米颗粒的微纳气泡,其特征在于,所述生物医学影像增强用纳米颗粒的粒径为5~100 nm,生物医学影像增强用纳米颗粒与生物医学用气体的浓度比值为(100 µg:1个)~(1 µg:100个)。
7.权利要求1所述的一种装载纳米颗粒的微纳气泡超声标记干细胞的方法,其特征在于,所述方法步骤如下:首先将装载纳米颗粒的微纳气泡与干细胞均匀混合,然后通过磁场或超声场进行物理场调控装载纳米颗粒的微纳气泡与干细胞相互作用和结合,实现微纳气泡或气泡破裂释放纳米颗粒标记干细胞。
8.根据权利要求7所述的一种装载纳米颗粒的微纳气泡超声标记干细胞的方法,其特征在于,所述超声场为超声波,所述超声波的发射选用平阵探头或聚焦探头,频率0.2~3MHz,声强为0.05~2.5 MPa,超声作用时间0.25~30 min;所述磁场为静磁场,矫顽力为10~25Oe,表面磁感应强度为10~1000 mT,磁场作用时间 20~40 min。
9.根据权利要求7所述的一种装载纳米颗粒的微纳气泡超声标记干细胞的方法,其特征在于,所述干细胞为神经干细胞、间充质干细胞或者诱导性多能干细胞。
10.权利要求1所述的一种装载纳米颗粒的微纳气泡在制备标记干细胞、超声或磁场引导干细胞靶向病变组织、利用生物医学成像技术对干细胞进行在体成像和示踪试剂中的应用。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113363040A (zh) * | 2021-05-28 | 2021-09-07 | 东南大学 | 一种基于磁热效应诱导界面自组装制备磁性脂质气泡的方法 |
CN117643621A (zh) * | 2023-10-27 | 2024-03-05 | 江苏省人民医院(南京医科大学第一附属医院) | 一种溶栓药PLT-r-SAK及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101912622A (zh) * | 2010-08-11 | 2010-12-15 | 东南大学 | 用于磁共振成像和血压监测的靶向微气泡探针及其制备方法 |
CN102776237A (zh) * | 2012-06-12 | 2012-11-14 | 西安交通大学 | 一种空化气泡介导的细胞激光转染方法 |
CN103243073A (zh) * | 2013-05-13 | 2013-08-14 | 东南大学 | 用于将纳米颗粒输入细胞的载体系统及方法 |
-
2018
- 2018-06-29 CN CN201810700249.1A patent/CN108939094A/zh active Pending
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101912622A (zh) * | 2010-08-11 | 2010-12-15 | 东南大学 | 用于磁共振成像和血压监测的靶向微气泡探针及其制备方法 |
CN102776237A (zh) * | 2012-06-12 | 2012-11-14 | 西安交通大学 | 一种空化气泡介导的细胞激光转染方法 |
CN103243073A (zh) * | 2013-05-13 | 2013-08-14 | 东南大学 | 用于将纳米颗粒输入细胞的载体系统及方法 |
Non-Patent Citations (4)
Title |
---|
FANG YANG ET AL: ""Silver Nanoparticle-Embedded Microbubble as a Dual-Mode Ultrasound and Optical Imaging Probe"", 《ACS APPL. MATER. INTERFACES》 * |
FANG YANG ET AL: ""Superparamagnetic iron oxide nanoparticle-embedded encapsulated microbubbles as dual contrast agents of magnetic resonance and ultrasound imaging"", 《BIOMATERIALS》 * |
YOUNG IL YOON ET AL: ""Smart gold nanoparticle-stabilized ultrasound microbubbles as cancer theranostics"", 《J. MATER. CHEM. B》 * |
YU-HSIN WANG ET AL: ""Synergistic delivery of gold nanorods using multifunctional microbubbles for enhanced plasmonic photothermal therapy"", 《SCIENTIFIC REPORTS》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113363040A (zh) * | 2021-05-28 | 2021-09-07 | 东南大学 | 一种基于磁热效应诱导界面自组装制备磁性脂质气泡的方法 |
CN117643621A (zh) * | 2023-10-27 | 2024-03-05 | 江苏省人民医院(南京医科大学第一附属医院) | 一种溶栓药PLT-r-SAK及其制备方法 |
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