CN114469894A - 硫酸多糖-叶酸偶联物合成纳米颗粒的制备 - Google Patents
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Abstract
本发明的硫酸多糖‑叶酸偶联物合成纳米颗粒的制备,将脱氧胆酸溶于蒸馏水中,再分别加入1.2个脱氧胆酸当量的1‑(3‑二甲基氨基丙基)‑3‑乙基碳二亚胺和N‑羟基丁二酰亚胺,使其与硫酸多糖中的氨基反应形成酰胺键,将活化后的脱氧胆酸,加入硫酸多糖‑叶酸偶联物溶液中充分混合,在磷酸盐缓冲液中沉淀制得硫酸多糖‑叶酸复合物,将反应后的复合物在水中透析,冻干,将改性后的硫酸多糖‑叶酸复合物溶解在磷酸盐缓冲液中缓慢摇晃,然后用声波降解法超声,使复合物在反应条件下自组装形成纳米颗粒,将药物运送到癌细胞表面,使药物在肿瘤中发挥作用,使全身的毒副作用降到最低,同时硫酸多糖‑叶酸还可以活化免疫细胞,进而对癌细胞进一步产生杀伤。
Description
技术领域
本发明涉及到硫酸多糖-叶酸偶联物合成纳米颗粒的制备。
背景技术
当今治疗肿瘤的方法,除了手术切除实体病灶之外,化疗、放疗以及靶向药物也得到广泛的应用。然而这些方法虽能在一定程度上控制癌症的发展,但后续问题还是层出不穷。就化疗或放疗来说,由于其缺乏特异性,毒性过大,损伤免疫系统,会在杀死肿瘤细胞的同时杀死健康细胞,严重影响病人的生存质量。因此,如何高效的将抗癌药物输送到病灶,针对性治疗癌症的新方法——靶向给药体系,便应运而生。
发明内容
本发明旨在于克服现有技术的不足,提供了一种硫酸多糖-叶酸偶联物合成纳米颗粒的制备,其以硫酸多糖-叶酸纳米颗粒的制备作为靶向给药体系为切入点,通过纳米颗粒活化免疫细胞的途径,实现纳米颗粒的靶向能力,将有助于开发硫酸多糖的药物功能,也可为硫酸多糖在杀灭癌细胞上提供新思路。
本发明的硫酸多糖-叶酸偶联物合成纳米颗粒的制备,是通过下列步骤实现的:
a、脱氧胆酸的活化:将脱氧胆酸溶于蒸馏水中,脱氧胆酸和蒸馏水的体积比为0.5~1: 0.5~1,再分别加入1~1.2个脱氧胆酸当量的1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和N-羟基丁二酰亚胺,使其与硫酸多糖中的氨基反应形成酰胺键;
b、硫酸多糖-叶酸偶联物的疏水性修饰:将硫酸多糖-叶酸偶联物溶于蒸馏水中,硫酸多糖和蒸馏水的质量浓度为5~10% W/V;再将a步骤得到活化后的脱氧胆酸,加入上述步骤得到的硫酸多糖-叶酸偶联物溶液中;活化后的脱氧胆酸溶液与硫酸多糖-叶酸偶联物溶液的反应摩尔比=0.01~0.02: 0.2~0.5,充分混合后,在磷酸盐缓冲液中沉淀制得硫酸多糖-叶酸复合物,以脱氧胆酸为疏水基,通过酰胺键将脱氧胆酸共价连接在硫酸多糖上;将反应后的复合物在过量的水中透析2~3天,冻干;
c、将改性后的硫酸多糖-叶酸复合物溶解在磷酸盐缓冲液中缓慢摇晃2~3h,然后用声波降解法在90W下超声2~10分钟,使复合物在反应条件下自组装形成纳米颗粒。
作为本发明的进一步改进,脱氧胆酸与硫酸多糖-叶酸偶联物的反应比为0.0115:0.230 mol/mol。
本发明的硫酸多糖-叶酸偶联物合成纳米颗粒的制备,是以硫酸多糖为主体的靶向给药体系,利用硫酸多糖与叶酸的偶联物自组装合成纳米颗粒来装载抗癌药物,将药物定向地运送到叶酸受体高度表达的癌细胞表面,使药物在肿瘤中发挥最大作用,而全身的毒副作用降到最低,同时硫酸多糖-叶酸还可以活化免疫细胞,进而对癌细胞进一步产生杀伤。利用这种方法不仅能有效地杀死肿瘤、抑制肿瘤进化,而且毒副作用相对较轻、可控,复发率低。
附图说明
图1为本发明的纳米颗粒对NK细胞和HeLa细胞的增殖。
具体实施方式
本发明中使用到的硫酸多糖-叶酸偶联物,是通过下列方法制得的:
a、将硫酸多糖充分溶于二甲基亚砜中,备用;其中,硫酸多糖与二甲基亚砜的质量浓度为10~15% W/V;
b、将0.3~0.5硫酸多糖当量的叶酸、二环己基碳二亚胺和4-二甲氨基吡啶以0.5~1: 0.5~1: 0.25~0.5的质量比溶于无水二甲基亚砜中,在20~35 ℃、避光条件下加入的氮气冲洗搅拌20~40 分钟,得到活化后的叶酸,备用;其中,叶酸、二环己基碳二亚胺和4-二甲氨基吡啶之和与无水二甲基亚砜质量浓度为10~15% W/V;
c、再将a步骤得到的硫酸多糖溶液缓慢滴加到b步骤得到的活化后的叶酸溶液中,滴加完成后在20~80 ℃、避光条件下持续搅拌6~24 h,待反应完成后,离心去除副产物,并在室温条件将上清液在35~50 ℃下磷酸盐缓冲液中透析2~3天后,再在用蒸馏水透析1~2天,透析后,通过离心除去过量的未反应的游离叶酸,再通过冻干获得硫酸多糖-叶酸偶联物。
实施例1
本发明的硫酸多糖-叶酸偶联物合成纳米颗粒的制备,是通过下列步骤实现的:
a、脱氧胆酸的活化:将脱氧胆酸溶于蒸馏水中,脱氧胆酸和蒸馏水的体积比为0.5~1: 0.5~1,再加入1~1.2个脱氧胆酸当量的1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和1~1.2个脱氧胆酸当量的N-羟基丁二酰亚胺,使其与硫酸多糖中的氨基反应形成酰胺键;
b、硫酸多糖-叶酸偶联物的疏水性修饰:将硫酸多糖-叶酸偶联物溶于蒸馏水中,硫酸多糖和蒸馏水的质量浓度为5~10% W/V;再将a步骤得到活化后的脱氧胆酸,加入上述步骤得到的硫酸多糖-叶酸偶联物溶液中;活化后的脱氧胆酸溶液与硫酸多糖-叶酸偶联物溶液的反应摩尔比=0.01~0.02: 0.2~0.5,充分混合后,在磷酸盐缓冲液中沉淀制得硫酸多糖-叶酸复合物,以脱氧胆酸为疏水基,通过酰胺键将脱氧胆酸共价连接在硫酸多糖上;将反应后的复合物在过量的水中透析2~3天,冻干;
c、将改性后的硫酸多糖-叶酸复合物溶解在磷酸盐缓冲液中缓慢摇晃2~3h,然后用声波降解法在90W下超声2~10分钟,使复合物在反应条件下自组装形成纳米颗粒,纳米粒子在4 ℃保存1个月后,通过测量颗粒的大小来评估配方的稳定性。
实施例2
本发明的硫酸多糖-叶酸偶联物合成纳米颗粒的制备,是通过下列步骤实现的:
a、脱氧胆酸的活化:将脱氧胆酸溶于蒸馏水中,脱氧胆酸和蒸馏水的体积比为1:1,再分别加入1.2个脱氧胆酸当量的1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和N-羟基丁二酰亚胺,使其与硫酸多糖中的氨基反应形成酰胺键;
b、硫酸多糖-叶酸偶联物的疏水性修饰:将硫酸多糖-叶酸偶联物溶于蒸馏水中,硫酸多糖和蒸馏水的质量浓度为5~10% W/V;再将a步骤得到活化后的脱氧胆酸,加入上述步骤得到的硫酸多糖-叶酸偶联物溶液中;活化后的脱氧胆酸溶液与硫酸多糖-叶酸偶联物溶液的反应摩尔比=0.0115: 0.230,充分混合后,在磷酸盐缓冲液中沉淀制得硫酸多糖-叶酸复合物,以脱氧胆酸为疏水基,通过酰胺键将脱氧胆酸共价连接在硫酸多糖上;将反应后的复合物在过量的水中透析3天,冻干;
c、将改性后的硫酸多糖-叶酸复合物溶解在磷酸盐缓冲液(pH=7.4)中缓慢摇晃2~3h,然后用声波降解法在90W下超声2分钟(为避免影响多糖结构,超声时间不易过长),使复合物在反应条件下自组装形成纳米颗粒,纳米粒子在4 ℃保存1个月后,通过测量颗粒的大小来评估配方的稳定性。
利用实施例2的方法制得的硫酸多糖-叶酸偶联物合成纳米颗粒对本发明性能做进一步说明:
1、硫酸多糖-叶酸纳米颗粒对NK细胞的增殖实验:自然杀伤细胞(NK)在α-MEM中培养,人宫颈癌细胞(HeLa)细胞在10% FBS的RPMI1640培养基中培养,两种细胞均在37℃, 5%CO2条件下培养。
通过前期实验方法(参考前期已完成的部分研究工作)开展该偶联物对NK细胞和HeLa细胞的增殖实验,并用下列公式1计算出该偶联物对NK细胞的增殖百分比:
实验结果证明硫酸多糖-叶酸偶联物对两种细胞均无毒性。此外,对NK细胞有显著的增殖能力,自身对HeLa细胞无任何杀伤能力,说明该偶联物保留了硫酸多糖的免疫增强能力,如图1所示。
图1中,横坐标分表代表纯化后的硫酸多糖(F2)、三种不同叶酸浓度的硫酸多糖-叶酸偶联物(F2-FA-Low (18.6%)、F2-FA-Medium (32.2%)、F2-FA-High (56.8%)),Medium为空白对照组。由图1实验结果可知,以上硫酸多糖及硫酸多糖-叶酸偶联物在 100 μg/mL浓度下对NK细胞和HeLa细胞有轻微的增殖能力,说明硫酸多糖-叶酸偶联物对两种细胞均无直接毒性作用(a、b、ab代表显著性分析结果)。
2、硫酸多糖-叶酸偶联物对HeLa细胞的靶向实验:靶向细胞试验通过化学和荧光成像两种方法确定。
(1)化学显色方法:为了定量细胞的靶向能力,将HeLa细胞用偶联物样品(200 μg/ml)处理6h。使用紫外分光光度计在363nm处测定上清液中的叶酸含量。结合下列公式2计算:
通过上清液中的叶酸含量减少,可以初步说明硫酸多糖-叶酸对HeLa细胞上的叶酸受体具有靶向结合能力。
(2)荧光成像方法:选取FITC作为标记偶联物的荧光剂。将一定量的偶联物(10 w/v%)在50℃下溶解于DMSO中,然后在遮光条件下冲入氮气搅拌,加入微量的FITC处理1h,使FITC结合在偶联物上。然后,将反应混合物用蒸馏水透析(3500Da),并将混合溶液以10000rpm离心10min去除未反应的FITC。再次将收集的上清液用蒸馏水透析,直到没有FITC紫外吸收峰为止。最后,通过冷冻干燥收集荧光染色后的偶联物。利用高速激光共聚焦高内涵流式细胞分析仪(CQ1)进行细胞成像实验进一步验证其靶向能力。将HeLa细胞置于96孔板中培养,并用FITC-偶联物(6 µg/mL)处理2 h。
用CQ1系统分析观察,通过细胞3D成像,可以证明随着偶联物中叶酸浓度的升高,对HeLa细胞上叶酸受体的靶向能力也越大,说明偶联物保留了叶酸对叶酸受体的靶向能力,从而证明了偶联物对HeLa细胞具有靶向能力。
3、多糖-叶酸偶联物合成纳米颗粒的靶向给药系统构建
通过纳米颗粒中的叶酸靶向能力以及高渗透长滞留效应(EPR),可以使该纳米颗粒定向的聚集在肿瘤病灶中,激活免疫细胞(NK细胞)的同时通过癌细胞自身的内吞作用释放装载的药物,双重作用下杀灭癌细胞,评价该纳米颗粒是否可以作为新型靶向给药系统的潜力。实验方法如下:
(1)、药物装载试验:筛选癌症治疗药物后,溶解在二甲基甲酰胺(DMF)溶液中,再将一定量的纳米颗粒加入到溶液中。室温震荡24h后,悬浮液在10000rpm下离心10min,弃掉上清液,移除未被吸附的药物,沉淀用DMF冲洗三遍。然后,将上清液与冲洗液合并,利用紫外分光光度计测定药物含量。吸附在载体材料中的药物含量等于总药物含量出去合并液中的药物含量即为其药物装载量。
(2)、药物释放试验:采用透析法研究药物的体外释放行为。选取PBS (pH=7.4)作为释放介质考察载体材料对药物的释放行为。首先,称取一定量的的纳米颗粒分散于5ml缓冲液中,制备成载药溶液,将其装入截留分子量为3500Da的透析袋中。然后,将透析袋浸润在缓冲液中,37℃恒温水平震荡。每个一段时间取样一次,并补充同样体积的新鲜缓冲液。由紫外分光光度计检测每次取样的释放液中药物的紫外吸收峰,计算药物的累计释放量,重复三次。
本发明通过制备基于硫酸多糖-叶酸的纳米颗粒来装载抗癌药物,形成靶向给药系统,当药物载体选择性的定向到癌细胞表面,除了硫酸多糖具有活化免疫细胞的功能外,还可通过癌细胞自身的内吞作用来释放抗癌药物,双重作用下杀死癌细胞,并且对机体几乎无毒性。
Claims (2)
1.硫酸多糖-叶酸偶联物合成纳米颗粒的制备,是通过下列步骤实现的:
a、脱氧胆酸的活化:将脱氧胆酸溶于蒸馏水中,脱氧胆酸和蒸馏水的体积比为0.5~1:0.5~1,再分别加入1~1.2个脱氧胆酸当量的1-(3-二甲基氨基丙基)-3-乙基碳二亚胺和N-羟基丁二酰亚胺,使其与硫酸多糖中的氨基反应形成酰胺键;
b、硫酸多糖-叶酸偶联物的疏水性修饰:将硫酸多糖-叶酸偶联物溶于蒸馏水中,硫酸多糖和蒸馏水的质量浓度为5~10% W/V;再将a步骤得到活化后的脱氧胆酸,加入上述步骤得到的硫酸多糖-叶酸偶联物溶液中;活化后的脱氧胆酸溶液与硫酸多糖-叶酸偶联物溶液的反应摩尔比=0.01~0.02: 0.2~0.5,充分混合后,在磷酸盐缓冲液中沉淀制得硫酸多糖-叶酸复合物,以脱氧胆酸为疏水基,通过酰胺键将脱氧胆酸共价连接在硫酸多糖上;将反应后的复合物在过量的水中透析2~3天,冻干;
c、将改性后的硫酸多糖-叶酸复合物溶解在磷酸盐缓冲液中缓慢摇晃2~3h,然后用声波降解法在90W下超声2~10分钟,使复合物在反应条件下自组装形成纳米颗粒。
2.如权利要求1所述的硫酸多糖-叶酸偶联物合成纳米颗粒的制备,其特征在于脱氧胆酸与硫酸多糖-叶酸偶联物的反应比为0.0115: 0.230 mol/mol。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2006203314A1 (en) * | 2000-04-17 | 2006-08-24 | Fudan University | A complex between folic acid and polysaccharides, its preparation method and a pharmaceutical composition comprising said complex as active component |
KR20070092438A (ko) * | 2006-03-10 | 2007-09-13 | 가톨릭대학교 산학협력단 | 풀루란을 가진 나노자가응집체 및 이의 이용방법 |
CN102319436A (zh) * | 2011-08-17 | 2012-01-18 | 山东大学 | 叶酸修饰的o-羧甲基壳聚糖-脱氧胆酸复合物及其制备方法与应用 |
CN103524760A (zh) * | 2013-10-10 | 2014-01-22 | 江苏大学 | 一种脱氧胆酸基-氧化可德兰多糖纳米粒子及制备方法 |
CN104162166A (zh) * | 2014-06-06 | 2014-11-26 | 上海大学 | pH敏感性多糖纳米载药胶束及其制备方法 |
CN105380902A (zh) * | 2015-11-18 | 2016-03-09 | 山东大学 | 叶酸修饰的硫酸软骨素-脱氧胆酸聚合物及其合成方法与应用 |
-
2022
- 2022-02-10 CN CN202210125875.9A patent/CN114469894B/zh active Active
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2006203314A1 (en) * | 2000-04-17 | 2006-08-24 | Fudan University | A complex between folic acid and polysaccharides, its preparation method and a pharmaceutical composition comprising said complex as active component |
KR20070092438A (ko) * | 2006-03-10 | 2007-09-13 | 가톨릭대학교 산학협력단 | 풀루란을 가진 나노자가응집체 및 이의 이용방법 |
CN102319436A (zh) * | 2011-08-17 | 2012-01-18 | 山东大学 | 叶酸修饰的o-羧甲基壳聚糖-脱氧胆酸复合物及其制备方法与应用 |
CN103524760A (zh) * | 2013-10-10 | 2014-01-22 | 江苏大学 | 一种脱氧胆酸基-氧化可德兰多糖纳米粒子及制备方法 |
CN104162166A (zh) * | 2014-06-06 | 2014-11-26 | 上海大学 | pH敏感性多糖纳米载药胶束及其制备方法 |
CN105380902A (zh) * | 2015-11-18 | 2016-03-09 | 山东大学 | 叶酸修饰的硫酸软骨素-脱氧胆酸聚合物及其合成方法与应用 |
Non-Patent Citations (2)
Title |
---|
CHANGSHENG LI 等: "Preparation and characterization of folic acid conjugated sulfated polysaccharides on NK cell activation and cellular uptake in HeLa cells", 《CARBOHYDRATE POLYMERS》 * |
CHANGSHENG LI 等: "Preparation and characterization of folic acid conjugated sulfated polysaccharides on NK cell activation and cellular uptake in HeLa cells", 《CARBOHYDRATE POLYMERS》, vol. 254, 15 February 2021 (2021-02-15), pages 2 * |
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