CN105126127B - 一种结肠癌核磁共振多功能造影剂的制备方法 - Google Patents
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Abstract
本发明公开了一种结肠癌核磁共振多功能造影剂的制备方法。将染料标记后的结肠癌肿瘤靶向多肽(TCP‑1)与磁性纳米载体结合,一方面具体通过Cy5.5有机染料标记TCP‑1多肽,并将N端修饰为炔基,合成炔基修饰的TCP‑1‑Cy5.5。另一方面,合成叠氮修饰的均一性氧化铁纳米粒子(Azide‑SPIO),最终将两者通过点击化学偶联制备多功能造影剂(SPIO‑TCP‑1‑Cy5.5)。本发明研制一种针对结肠癌的早期诊断的新型造影剂,TCP‑1将引导纳米粒子特异性地结合并进入肿瘤的新生血管细胞,用磁共振显影联合远红外荧光成像将可以实现小至几个毫米的早期肿瘤检测。
Description
技术领域
本发明属于纳米生物医药技术领域,涉及一种结肠癌核磁共振多功能造影剂的制备,具体涉及一种具有结肠癌肿瘤识别功能的TCP-1多肽与磁性氧化铁纳米粒子的结合,制备出一种新型的多功能靶向性肿瘤分子影像探针,旨在提供一种无创性和灵敏的早期诊断结肠癌的T2造影剂。
背景技术
近年来,造影剂辅助的核磁共振成像是目前肿瘤诊断的最好方法之一。但是由于核磁共振成像内在的低灵敏性以及造影剂的非特异性,导致肿瘤早期诊断较为困难。在过去20年,已开发了各种无机材料作为造影剂。在众多纳米材料中,磁性纳米粒子由于具有良好的生物安全性、生物相容性以及表面的多功能性,已经成为生物医学中实际应用最成功的纳米材料之一。
氧化铁纳米粒子(Fe3O4或Fe2O3)是一种网状内皮系统的对比剂,可用于肝、脾、淋巴结、骨髓等富含网状内皮细胞的组织和器官的磁共振信号增强。通过被动传递机制,氧化铁纳米粒子可以被细胞网状内皮系统的选择性摄取,从而能够大大缩短在肝脏、脾和骨髓的T2弛豫时间而被检测到。到目前为止,全世界已经有多种商品化氧化铁纳米颗粒造影剂上市。
构建靶向性肿瘤分子影像探针,最重要的是发现及合成对某种特定肿瘤具有特异性亲和力的靶向分子。这种靶向分子需要能够引导影像探针及药物分子,甚至是纳米颗粒进入特定的细胞,而且必须要区分健康组织和患病组织。小于20个氨基酸的短肽是非常有应用前景的靶向性分子。
因此,将多功能磁性纳米颗粒与可以有效识别肿瘤的靶向性分子进行偶联,进而获得可主动识别肿瘤的多功能磁共振分子影像探针,来有效实现对微小肿瘤的早期诊断,已成为肿瘤MR成像诊断的一个重要的发展趋势。
本发明通过将具有结肠癌识别功能的TCP-1多肽与荧光染料偶联后与磁性纳米载体结合,使磁性纳米载体具有分子靶向性功能,研制一种针对结肠癌的早期诊断的新型造影剂。
发明内容
本发明所要解决的技术问题是针对目前结肠癌的特异性造影剂在临床上还是空白,针对这一迫切的需要,提供第一个无创性和灵敏的早期诊断结肠癌的T2造影剂。
本发明解决其技术问题所采用的技术方案是:
(一)合成炔基(Alkyne)修饰的TCP-1-Cy5.5
将固相合成多肽TCP-1侧链标记Cy5.5,然后N端脱保护后加入丙炔酸,在缩合剂的作用下将N端修饰为炔烃。
(二)合成叠氮修饰的均一性Azide-SPIO
(1)合成氨基修饰的SPIO
采用化学沉淀法制备Fe3O4纳米粒子,将纳米粒子与氢氧化钠和环氧氯丙烷混合后,加入氨水,反应24小时后得到氨基修饰的SPIO。
(2)合成叠氮修饰的SPIO(Azide-SPIO)
氨基修饰的SPIO与Azide-dPEG4-NHS混合反应后,通过superdex200层析柱分离纯化,得到Azide-SPIO。
(三)炔基修饰的TCP-1-Cy5.5与Azide-SPIO通过点击化学偶联
SPIO表面的叠氮与靶向多肽TCP-1-Cy5.5的炔基通过点击化学连接。将Azide-SPIO与过量靶向多肽混合,加入Bathocuproinedisulfonic acid(BCS),CuSO4和Sodiumascorbate,室温反应过夜。透析进行纯化得到SPIO-TCP-1-Cy5.5。
附图说明
图1:多功能纳米材料SPIO-TCP-1-Cy5.5的合成示意图。
图2:炔基修饰的TCP-1-Cy5.5的合成步骤示意图。
图3:合成叠氮修饰的SPIO示意图。
图4:炔基修饰的TCP-1-Cy5.5与Azide-SPIO通过点击化学偶联示意图。
具体实施方式
本发明将就以下实施例作进一步说明,但应了解的是,这些实施例仅为例示说明之用,而不应被解释为本发明实施的限制。
实施例1合成多功能造影剂SPIO-TCP-1-Cy5.5
(一)合成炔基(Alkyne)修饰的TCP-1-Cy5.5
a)采用Fmoc化学固相多肽合成,使用溶胀性非常好的 树脂,用5倍过量的Fmoc保护的氨基酸和缩合试剂(HBTU/HOBt)完成多肽序列。
b)将侧链Mtt保护的赖氨酸(K)用1%三氟乙酸(TFA)选择性地脱保护,加入Cy5.5free acid,EDC和HOBt作为缩合试剂,室温过夜反应偶联Cy5.5。
c)多肽N端用20%哌啶(Piperidine)脱保护,加入丙炔酸(propiolic acid),以N,N’-二异丙基碳化二亚胺(DIC)为缩合试剂,将N端修饰为炔烃。
d)用95%的TFA(以及自由基清除剂)将多肽从树脂上切割下来,用乙醚沉淀,得到的粗肽用C18反相高效液相色谱法(RF-HPLC)分析并分离纯化。然后将线性肽在空气中氧化形成环状结构,通过RF-HPLC和质谱来证实,最终产品冻干和储存在-20℃。详细的合成计划如图2所示。
(二)合成叠氮修饰的均一性Azide-SPIO
(1)合成氨基修饰的SPIO
根据文献报道的方法,采用化学沉淀法制备Fe3O4纳米粒子。0.73g FeCl2和1.97gFeCl3分别溶解于12.5mL去离子水中,冷却到4℃,待用。将25g葡聚糖(Dextran,T10)溶解于50mL去离子水,冷却到4℃并用氮气脱气1小时,加入FeCl2和FeCl3的水溶液。用磁力搅拌器搅拌,同时滴加28%氨水15mL,升温至90℃,反应1小时,得到黑褐色悬浊液。冷却后离心,弃去沉淀。将上清液放置透析袋中透析24小时(截留分子量100kD)。通过改变反应条件,可制备不同粒径的氧化铁纳米粒子。
将透析后的产物与25%的10M氢氧化钠和33%环氧氯丙烷混合24小时后,加入25%氨水,再反应24小时后得到氨基修饰的SPIO。
(2)合成叠氮修饰的SPIO(Azide-SPIO)
如图3所示,将氨基修饰的SPIO与Azide-dPEG4-NHS混合(摩尔比1:100),溶解于0.1M磷酸钠缓冲液(pH9)中,反应8小时后,通过superdex200层析柱分离纯化,得到Azide-SPIO。
(三)炔基修饰的TCP-1-Cy5.5与Azide-SPIO通过点击化学偶联
SPIO的表面的叠氮与靶向多肽TCP-1-Cy5.5的炔基通过点击化学连接(图4)。将Azide-SPIO与过量靶向多肽混合,加入5mM Bathocuproinedisulfonic acid(BCS),1mMCuSO4和5mM Sodium ascorbate,室温反应过夜。反应结束后,通过透析(截留分子量100KD)进行纯化,除去未反应的多肽和其他小分子反应物,得到SPIO-TCP-1-Cy5.5。
实施例2合成多功能造影剂SPIO-TCP-1-ATTO 590
合成步骤如实施例1相同,荧光染料为ATTO 590,得到新型多功能造影剂SPIO-TCP-1-ATTO 590。
以上述依据本发明的理想实施例为启示,通过上述的说明内容,相关工作人员完全可以在不偏离本项发明技术思想的范围内,进行多样的变更及修改。本项发明的技术性范围并不局限于说明书上的内容,必须要根据权利要求范围来确定其技术范围。
Claims (4)
1.一种结肠癌核磁共振多功能造影剂的制备方法,其特征在于,将染料标记后的结肠癌肿瘤靶向多肽与磁性纳米载体结合,通过近红外染料Cy5.5标记TCP-1多肽,并将N端修饰为炔基,合成炔基修饰的TCP-1-Cy5.5,然后合成叠氮修饰的均一性氧化铁纳米粒子(Azide-SPIO),最终将两者通过点击化学偶联制备多功能造影剂(SPIO-TCP-1-Cy5.5)。
2.根据权利要求1所述的一种结肠癌核磁共振多功能造影剂的制备方法,其特征在于,所述多肽为TCP-1为环状多肽CTPSPFSHC,这个多肽序列在体内可以特异性地结合结肠肿瘤新生的血管细胞,即CD31+阳性细胞。
3.根据权利要求1所述的一种结肠癌核磁共振多功能造影剂的制备方法,其特征在于,所述磁性纳米载体为氧化铁纳米粒子。
4.根据权利要求1所述的一种结肠癌核磁共振多功能造影剂的制备方法,其特征在于,所述结合方法为点击化学偶联,具体将多肽N端修饰为炔基,SPIO表面修饰叠氮。
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Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070148095A1 (en) * | 2005-12-23 | 2007-06-28 | Industrial Technology Research Institute | Fluorescent magnetic nanoparticles with specific targeting functions |
WO2008054523A2 (en) * | 2006-05-04 | 2008-05-08 | Emory University | Nanostructures, methods of synthesizing thereof, and methods of use thereof |
CN102397564A (zh) * | 2010-09-19 | 2012-04-04 | 复旦大学 | 一种肿瘤靶向诊断核磁共振造影剂及其制备方法 |
CN102412046A (zh) * | 2011-08-17 | 2012-04-11 | 上海交通大学 | 富集叠氮标记生物大分子的磁性纳米材料及其制备与应用 |
CN102462847A (zh) * | 2010-11-15 | 2012-05-23 | 杨静雯 | 新型肿瘤靶向造影剂 |
CN102471371A (zh) * | 2009-07-29 | 2012-05-23 | 香港中文大学 | 用于肿瘤血管系统的归巢肽 |
CN102961761A (zh) * | 2012-11-02 | 2013-03-13 | 常州大学 | 一种用于结肠癌肿瘤组织识别的量子点靶向探针及其制备方法 |
CN103505746A (zh) * | 2013-06-05 | 2014-01-15 | 华中科技大学 | 一种胶质瘤靶向磁共振和荧光双模式成像对比剂及制备方法 |
-
2015
- 2015-10-14 CN CN201510660787.9A patent/CN105126127B/zh active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20070148095A1 (en) * | 2005-12-23 | 2007-06-28 | Industrial Technology Research Institute | Fluorescent magnetic nanoparticles with specific targeting functions |
WO2008054523A2 (en) * | 2006-05-04 | 2008-05-08 | Emory University | Nanostructures, methods of synthesizing thereof, and methods of use thereof |
CN102471371A (zh) * | 2009-07-29 | 2012-05-23 | 香港中文大学 | 用于肿瘤血管系统的归巢肽 |
CN102397564A (zh) * | 2010-09-19 | 2012-04-04 | 复旦大学 | 一种肿瘤靶向诊断核磁共振造影剂及其制备方法 |
CN102462847A (zh) * | 2010-11-15 | 2012-05-23 | 杨静雯 | 新型肿瘤靶向造影剂 |
CN102412046A (zh) * | 2011-08-17 | 2012-04-11 | 上海交通大学 | 富集叠氮标记生物大分子的磁性纳米材料及其制备与应用 |
CN102961761A (zh) * | 2012-11-02 | 2013-03-13 | 常州大学 | 一种用于结肠癌肿瘤组织识别的量子点靶向探针及其制备方法 |
CN103505746A (zh) * | 2013-06-05 | 2014-01-15 | 华中科技大学 | 一种胶质瘤靶向磁共振和荧光双模式成像对比剂及制备方法 |
Non-Patent Citations (1)
Title |
---|
Conjugation of Transferrin to Azide-Modified CdSe/ZnS Core–Shell Quantum Dots using Cyclooctyne Click Chemistry;Christine Schieber,et al,;《Angew.chem.》;20120920;第51卷;第10523-10527页 * |
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