CN108815524B - 透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂及其制备方法 - Google Patents
透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂及其制备方法。所述光热治疗剂包括载药相变材料核心、聚吡咯外壳以及吸附在聚吡咯壳层表面的透明质酸。本发明制备的光热治疗剂形态均一,大小均匀,粒径约为233nm,可靶向作用于肿瘤部位。同时,其相变材料核心可响应于温度变化,呈现温度敏感性药物释放。而且,透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂还具有良好的光热转换效率和光声显影效果,当负载抗肿瘤药物之后还具有靶向肿瘤化疗‑光热治疗的协同作用,提高了肿瘤治疗效果,具有良好的应用前景。
Description
技术领域
本发明涉及医疗药物领域,具体涉及透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂及其制备方法。
背景技术
近年来,刺激响应性纳米给药系统在肿瘤治疗研究领域越来越吸引研究者们的注意。触发刺激响应性纳米给药系统的刺激可以是内部的或者外部的。根据细胞内稳态,内部刺激可以为氧化还原、酶、pH等,外部刺激可以为磁共振,光,超声,温度,电场等。基于这些内部或外部刺激构建的抗肿瘤药物递送平台可通过改变药物代谢动力学和药效学参数,实现药物在病灶部位的可控释放,提高药物生物利用率,从而增强抗肿瘤疗效,并降低药物毒副作用。
有机相变材料(phase change materials,PCM),包括许多脂肪酸和脂肪醇,因其具有独特的温度敏感性,在药物控制释放领域有着潜在的应用价值而受到研究者的广泛关注。在这些PCM中,天然脂肪酸由于其无毒性,化学稳定性和生物相容性而特别具有吸引力。当脂肪酸被加热至熔点以上时,其迅速从固相变为液相,加速包封药物的溶解与释放。
近红外光敏剂在波长范围为700-900nm的近红外领域(near-infrared,NIR)具有良好的光吸收特性,可将光能转换为热效应,引起局部温度短暂性上升,实现定点杀伤肿瘤细胞。目前,文献已报道的光敏感纳米材料包括各种结构的金纳米粒子、碳纳米粒子以及硫化铜纳米粒子等,虽然这些无机纳米材料在前期研究中表现出显著的光热转换效率,但它们繁琐的合成工艺,不可生物降解以及潜在长期细胞毒性等问题阻碍其进一步的临床应用。相反,有机光敏材料,主要包含近红外染料,共轭聚合物和卟啉脂质体这几类,其不仅具有理想的光热转换能力,还具有优良的生物相容性和药物/基因递送能力。
在众多有机光敏剂中,高分子聚吡咯(Polypyrrole,PPY)展现出一些特殊性质,如良好的生物相容性,高效的光热转换能力以及出色的光稳定性能,这些特性使其在生物医学领域具有广泛的应用前景。由于具有疏水性质和π-π堆叠结构,聚吡咯纳米材料成为了递送疏水性药物(尤其是芳香族药物)的良好候选者。此外,近年的研究发现聚吡咯在近红外激发波长下能产生明显的光声信号,可作为潜在的光声造影剂用于肿瘤的光声成像和光热治疗。结合这些优异性能,聚吡咯有望在未来的医学领域实现肿瘤的可视化治疗。
透明质酸(hyaluronic acid,HA),作为一种天然高分子多糖,不仅具有良好的生物相容性、高黏弹性、可降解性及非免疫原性等优点,还能特异性黏附CD44过表达的多种恶性肿瘤细胞,通过受体-配体相互作用增强肿瘤细胞结合和内化HA纳米粒的效果。研究表明,以HA充当靶向基团的纳米载体可以选择性地引领药物进入靶部位(肿瘤部位),提高药物治疗疗效,同时减少不良反应的发生。
综上所述,开发新型的、高效安全的多功能载体用于增强药物抗肿瘤治疗具有重要的研究与应用价值。多功能药物递送系统由载药PCM核心,PPY外壳和吸附在PPY壳上的HA组成。该系统不仅具有良好的光热消融肿瘤的能力,而且还具有实时光声成像的潜能,因此具有广阔的应用前景。
发明内容
本发明的目的在于提供一种协同化疗-光热治疗的肿瘤靶向多功能光热治疗剂及其制备方法。制备得到的多功能光热治疗剂粒径较小,可通过EPR效应被动靶向或主动靶向作用于肿瘤部位。同时,其相变材料核心可响应于温度变化,呈现温度敏感性药物释放。而且,以聚吡咯作为外壳的光热治疗剂具有良好的光热转换效率和明显的光声显影效果。当负载抗肿瘤药物多西他赛之后还可以实现增强的靶向肿瘤化疗-光疗协同治疗,大大提高治疗效率,具有广阔的应用潜力。
本发明的目的可以通过以下技术方案实现,但本发明并不仅限于下述技术:
步骤1:称取一定量月桂酸和硬脂酸(w/w:4/1),溶解于共溶剂二氯甲烷中,搅拌均匀,得到相变材料溶液。
步骤2:称取适量的大豆磷脂和药物于圆底烧瓶中,加入一定量的步骤1得到的相变材料溶液,减压旋转蒸发成膜,然后加入一定量的蒸餾水,震荡使薄膜脱壁,得到载药相变材料脂质混悬液。
步骤3:将步骤2得到的载药相变材料脂质混悬液在50~55℃水浴超声处理2~5min,得到载药相变材料脂质纳米粒,将该纳米粒于4℃冷却。
步骤4:将步骤3得到的载药相变材料脂质纳米粒,在冰浴环境下搅拌10min,然后加入一定量的聚乙烯醇溶液和三氯化铁溶液和少量吡咯,反应一段时间后,得到聚吡咯包裹载药相变材料纳米粒。
步骤5:称取一定量的透明质酸,溶解于蒸馏水中,得到透明质酸溶液。然后将该溶液加入步骤4得到的聚吡咯包裹载药相变材料纳米粒,冰浴继续搅拌一段时间,离心收集产物,蒸馏水清洗3次,再重新水浴超声分散于蒸馏水中,得到透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂。
本发明采用纳米沉淀法和氧化-聚合法成功制备了透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂。该治疗剂对肿瘤具有主动靶向作用,能将化疗药物和光敏剂递送至肿瘤组织,实现药物在病灶部位的可控释放,并借助于红外激光高效消融肿瘤细胞,对正常组织毒性较小。这种协同化疗和光疗的肿瘤靶向药物递送系统,为肿瘤的治疗提供了新的方法。
附图说明
图1为本发明实例1中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的平均粒径图。
图2为本发明实例1中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的透射电镜图。
图3为本发明实例1中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的红外图谱。
图4为本发明实例2中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的光热效应图。
图5为本发明实例2中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的光声显影图。
图6为本发明实例2中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的细胞摄取图。
图7为本发明实例2中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的体外细胞毒性。
图8为本发明实例2中透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的肿瘤生长曲线图。
具体实施方式
以下结合附图实施例对本发明进行详细描述,但本发明并不仅限于下述实施例。
实施例1
1.载药相变材料脂质纳米粒的制备
将月桂酸和硬脂酸(w/w:4/1)溶解于二氯甲烷中配置浓度为4mg/mL相变材料溶液。精密称取30.0mg大豆磷脂和3.0mg多西他赛于10mL圆底烧瓶中,加入1.2mL上述相变材料溶液,随后蒸发成膜。然后,加入3.6mL蒸馏水,50℃水浴超声约2min,迅速冰浴冷却,得到载药相变材料脂质纳米粒。
2.聚吡咯包裹载药相变材料光热治疗剂的制备
将冷却的载药相变材料脂质纳米粒,在冰浴环境下搅拌10min,然后分别加入0.75mL的聚乙烯醇溶液(100mg/mL)和0.75mL三氯化铁溶液(150mg/mL),搅拌大约5min后,加入22μL吡咯,反应0.5-2h,得到聚吡咯包裹载药相变材料纳米粒。
3.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的制备
在聚合反应进行大约0.5h后,加入1mL透明质酸溶液(5.0mg/mL),继续冰浴搅拌3-4h,离心收集产物,蒸馏水清洗3次,再重新水浴超声分散于蒸馏水中,即得透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂。
将制备得到的透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂用蒸馏水稀释至特定浓度,采用马尔文粒度仪检测25℃条件下纳米粒的粒径分布,如图1所示,光热治疗剂的平均粒径为232.7±17.3nm。如图2所示,透射电镜下样品的形态特征为规整的球体结构。傅里叶紅外分光光度計验证了聚吡咯的成功包裹和透明质酸的成功修饰,如图3所示,(a)表示载相变材料脂质纳米粒,修饰聚吡咯后,在1642cm-1处出现了聚吡咯环上N-H键的变形振动峰,1540cm-1处的特征峰为聚吡咯环上C=C双键的骨架振动产生,这说明得到了聚吡咯包裹载药相变材料光热治疗剂(b)。在进一步吸附上透明质酸,得到透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂(c),在2840cm-1-2918cm-1、1727cm-1以及1400cm-1处出现了新的吸收峰,这些峰或许是C-H、C=O以及C-N伸缩振动产生的,此外,C=C峰和N-H峰也分別迁移移到1538cm-1和1667cm-1,这些数据说明透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂制备成功。
实施例2
1.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂体外光热效应检测
采用光纤耦合输出激光器考察透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂混悬液的光热效应,具体步骤如下:将样品用去离水稀释到不同浓度(0.25、0.5、1.0、2.0mg/mL),量取2mL不同浓度的纳米悬液于石英比色皿中,在功率密度1.0W/cm2的近红外激光(808nm)下辐照10分钟,同时记录样品的温度变化,以不加纳米混悬液的去离子水为空白对照。从图4可知,对照组温度变化不明显,这表明单纯的激光辐射不能显著升高温度。与之相反,纳米混悬液的升温性能呈现浓度依赖性,其浓度越高,温度上升越快。
2.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的体内外光声信号检测
采用小动物光声成像仪检测透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的体内外光声信号,步骤如下:取200μL纳米混悬液注入琼脂模型中,置于光声探测器件处,在700nm脉冲激发下记录超声波信号值变化,以PBS作为空白对照。为了进一步评估纳米混悬液体内的光声成像性能,选择4T1荷瘤Balb/c雌性小鼠为动物模型。图5为体内外光声信号图。实验结果与预期一致,在注入纳米混悬液后,光声显影效果显著性增强,其对应的光声成像图片变得更亮,表明本研究制备的纳米颗粒具有较强的光声信号响应值。因此,透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂混悬液作为光声造影剂用于体外光声成像是可行并有效的。而且,体内显影效果与体外一致。在注射纳米颗粒后,在肿瘤区域明显观察到光声信号增加,表明透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂混悬液在体内也具有有效的光声成像能力。
3.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的细胞摄取情况
研究表明A549肺癌细胞是CD44受体高表达细胞,本试验选择A549细胞为实验对象评估纳米制剂的内吞情况。在附有爬片的6孔板中接种5×104个细胞。待细胞铺满约80%时,吸取掉上清液,加入500μL含0.2mg/mL香豆素-6标记的聚吡咯包裹载药相变材料光热治疗剂和香豆素-6标记透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的培养基,孵育30min后,除去残留纳米制剂,3.7%多聚甲醛处理20min后,DAPI标记核位置,甘油封片后用倒置荧光显微镜观察摄取情况。图6反映了不同纳米制剂的细胞内摄取情况。香豆素-6是一种应用普遍的高灵敏荧光探针,呈现绿色荧光,用来标记细胞质,DAPI与细胞核中的DNA结合后使细胞核显示蓝色荧光。实验组(a)与对照组(b)相比,其在A549细胞中的荧光密度显著增强,这表明香豆素-6标记透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂对CD44过表达的A549细胞具有主动靶向性。
4.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的体外细胞毒性检测
采用MTT试验考察不同纳米制剂对A549细胞的细胞毒性,实验设置6个组(n=6),分别为多西他赛组、聚吡咯包裹载药相变材料光热治疗剂、受体饱和组、透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂、透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂+激光照射、纯激光照射,其中以不做任何处理的空白组作为对照组,默认存活率为100%,纯激光组仅进行同等功率同等时间的光照。A549细胞(每孔8000个细胞)接种于96孔培养板孵育过夜,分别用含不同药物浓度(5和25μg/mL)的不同制剂处理。在恒温孵箱中培养4h后,将光热组暴露于808nm红外激光(1.5W/cm2)下3min。继续培养24h后,PBS清洗细胞三次,在MTT溶液(5mg/mL)中继续孵育4h,加入150μL DMSO,采用酶标仪测定各个样品的吸光度值。为了考察纳米混悬液的靶向性,我们另外设置了受体饱和组,将细胞用游离HA(10mg/mL)预处理2h以阻断其细胞表面的受体。如图7所示,单纯的808nm红外激光照射没有明显的细胞毒性,这表明红外激光对正常细胞没有杀伤作用。从数据中可以看出,在没有激光照射的情况下,透明质酸修饰组的细胞抑制作用强于无配体修饰组,证实了透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂具有主动靶向A549细胞的能力。此外,在给予激光照射后纳米粒混悬液的存活率进一步降低,这归因于光疗与化疗协同作用的结果。同时原料药多西他赛组细胞活力并无明显差异,这表明纯激光并不能增加原料药的细胞毒性。对于受体阻断组,当细胞被高浓度(10mg/mL)游离透明质酸预处理2小时后,细胞存活率显著性降低,这或许是由于游离透明质酸饱和了细胞表面的CD44受体,抑制了纳米制剂的内化,降低了其治疗效果。
5.透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂的靶向肿瘤化疗-光疗协同治疗
采用4T1荷瘤小鼠作为动物模型,待瘤子平均体积约为138mm3时,将荷瘤小鼠随机分组,每组5只,从第0天起开始给药,每隔一天处理一次,每次瘤内给予50μL不同的纳米制剂(多西他赛:1.25mg/kg),激光组为纳米制剂处理24h后暴露于808nm激光下,输出功率为1.0W/cm2,照射时间为5min。如图8所示,在整个治疗期间,对照组的肿瘤生长速度最快,16天后的平均肿瘤体积约为1590±221mm3,这表明单纯的激光照射不会有效抑制肿瘤生长。原料药多西他赛组的肿瘤生长速率略微降低。与之相反,其余3个组均展示了不同程度的肿瘤生长抑制作用。其中透明质酸修饰组的肿瘤抑制效果强于无配体修饰组,说明透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂具有良好的主动靶向能力。此外,透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂+激光照射组具有更高的抑瘤效果,采用此方案处理小鼠后,肿瘤原始部位会出现黑色疤痕,大约14天后结痂脱落,这表明透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂+激光照射组具有良好的光疗和化疗协同肿瘤消融效果。
Claims (3)
1.一种透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂,其特征在于制备方法包括以下步骤:
(1)将重量比为4:1的月桂酸和硬脂酸溶解于二氯甲烷中,配置浓度为4mg/mL相变材料溶液,精密称取30.0mg大豆磷脂和3.0mg化疗药物多西他赛于10mL圆底烧瓶中,加入1.2mL上述相变材料溶液,随后蒸发成膜,然后加入3.6mL蒸馏水,50℃水浴超声2min,迅速冰浴冷却,得到载药相变材料脂质纳米粒;
(2)将冷却的载药相变材料脂质纳米粒,在冰浴环境下搅拌10min,然后分别加入0.75mL浓度为100mg/mL的聚乙烯醇溶液和0.75mL浓度为150mg/mL三氯化铁溶液,搅拌5min后,加入36.7mg吡咯,反应0.5-2h,得到聚吡咯包裹载药相变材料纳米粒;
(3)在聚合反应进行0.5h后,加入1mL浓度为5.0mg/mL的透明质酸溶液,继续冰浴搅拌3-4h,离心收集产物,蒸馏水清洗3次,再重新水浴超声分散于蒸馏水中,即得透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂。
2.如权利要求1所述的透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂,所述化疗药物还可以是紫杉醇、阿霉素、喜树碱、羟基喜树碱、顺铂或5-氟尿嘧啶。
3.如权利要求1所述的透明质酸修饰聚吡咯包裹载药相变材料光热治疗剂,其特征在于所述的光热治疗剂粒径为50~800nm。
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CN114601934B (zh) * | 2022-03-10 | 2023-06-13 | 北京大学第三医院(北京大学第三临床医学院) | 负载小干扰rna的可电荷反转光热纳米粒子及其制备和应用 |
CN115354412A (zh) * | 2022-08-31 | 2022-11-18 | 嘉兴自然三禾新材料科技有限公司 | 一种调温棉及其制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106178004A (zh) * | 2016-08-23 | 2016-12-07 | 国家纳米科学中心 | 一种磁性纳米诊疗剂及其制备方法和应用 |
CN107952070A (zh) * | 2017-11-17 | 2018-04-24 | 天津大学 | 双重成像引导的光热治疗多功能纳米杂化物及制备方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060051401A1 (en) * | 2004-09-07 | 2006-03-09 | Board Of Regents, The University Of Texas System | Controlled nanofiber seeding |
-
2018
- 2018-07-06 CN CN201810738648.7A patent/CN108815524B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN106178004A (zh) * | 2016-08-23 | 2016-12-07 | 国家纳米科学中心 | 一种磁性纳米诊疗剂及其制备方法和应用 |
CN107952070A (zh) * | 2017-11-17 | 2018-04-24 | 天津大学 | 双重成像引导的光热治疗多功能纳米杂化物及制备方法 |
Non-Patent Citations (7)
Title |
---|
A Eutectic Mixture of Natural Fatty Acids Can Serve as the Gating Material for Near-Infrared-Triggered Drug Release;Chunlei Zhu等;《Adv.Mater.》;20170905;第29卷;第1页摘要,第2页Scheme 1 * |
Combined photothermal and photodynamic therapy by hyaluronic acid-decorated polypyrrole nanoparticles;Tuan Hiep Tran等;《Nanomedicine》;20170602;第1页摘要,第3页Figure 1,第7页左栏最后1段至右栏第1段 * |
In Vitro and In Vivo Near-Infrared Photothermal Therapy of Cancer Using Polypyrrole Organic Nanoparticles;Kai Yang等;《Adv. Mater.》;20120822;第24卷;第5586-5592页 * |
Photoinduced Mild Hyperthermia and Synergistic Chemotherapy by One-Pot-Synthesized Docetaxel-Loaded Poly(lactic-co-glycolic acid)/Polypyrrole Nanocomposites;Jie Yuan等;《ACS Appl. Mater. Interfaces》;20160826;第8卷;第24445页摘要,第24448页Figure 1 * |
Polypyrrole-based nanotheranostics for activatable fluorescence imaging and chemo/photothermal dual therapy of triple-negative breast cancer;Dongjin Park等;《Nanotechnology》;20160323;第27卷;第1-12页 * |
Polypyrrole-Coated Perfluorocarbon Nanoemulsions as a Sono-Photoacoustic Contrast Agent;David S. Li等;《Nano Lett》;20170919;第17卷;第6184-6194页 * |
Synthesis and Properties of Phase Change Material-Polypyrrole Core-Shell Nanocapsules via Fe3+-Oxidative Miniemulsion Polymerization;Hyun Woog Ryu等;《Macromolecular Research》;20131231;第21卷(第3期);第298-301页 * |
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