CN112516312A - 一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法 - Google Patents
一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法 Download PDFInfo
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Abstract
本发明提出了一种超声成像/光敏治疗的多功能纳米探针的制备方法，主要通过将5‑HT3抗体偶联在壳聚糖上，制备高分子载体化合物；将载体化合物包裹氟碳化合物，形成氟碳纳米粒，同时将其与亲水性的光敏剂同时包裹于纳米粒中，形成氟碳、光敏剂的纳米粒。本发明所制备的纳米粒，5‑HT3抗体具有靶向肠道的功能、氟碳具有超声成像功能、光敏剂具有光动力疗法作用。制备工艺简单，所得的产物稳定性好。
Description
技术领域
本发明涉及生物化学领域，具体涉及一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法。
背景技术
消化不良及胃肠道功能紊乱是一组由腹痛、腹胀、早饱、嗳气、恶心等一系列上消化道症状组成的异质性综合征，主要包括胃排空功能异常及小肠黏膜化学环境的改变。但目前传统影像学检查手段难以同时完成对胃排空功能及肠粘膜功能的检测。近年来分子影像学及纳米技术的迅速发展，新型靶向对比剂或为此提供了可能。目前已知胃肠黏膜中传入通路5-羟色胺（5-HT）信号通路与内脏高敏感反应密切相关。
5-HT及其受体广泛分布于胃肠道。5-HT3受体属于配体门控阳离子通道家族，现已分离5-HT3A、5-HT3B、5-HT3C、5-HT3D和5-HT3E 5种受体亚基。5-HT3受体基因型与肠易激综合征发病机制紧密联系。因此，5-HT3可以作为肠道紊乱的靶向受体，从而制备出肠道疾病靶向诊断的制剂。
发明内容
为了解决现有技术中存在的上述问题，本发明目的在于提供一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法。
本发明目的通过下述方案实现：一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于通过将5-HT3抗体偶联在壳聚糖上，制备高分子载体化合物；将载体化合物包裹氟碳化合物，形成氟碳纳米粒，同时将其与亲水性的光敏剂同时包裹于纳米粒中，形成氟碳、光敏剂的纳米粒，制备过程包括如下步骤：
（1）壳聚糖的改性
在1份壳聚糖中，加入1份助溶的乙醇和10份二次水，同时加入1份N-羟基琥珀酰亚胺（NHS）和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐（EDC），再加入0.5份5-HT3抗体。室温下搅拌24小时后，将产物过滤，离心，洗涤，制成5-HT3抗体改性的壳聚糖；
（2）多功能纳米探针的制备
将30-40份的5-HT3抗体改性的壳聚糖溶解于100份的水中，然后加入助表面活性剂20-30份、增溶剂30-40份、盐10-15份、光敏剂10-20份，超声振荡至混合均匀、静置2小时，配制成乳液；加入10-15份氟碳示踪剂，在4℃及惰性气氛下搅拌5-30分钟，冷却至25℃，静置静置24-48小时，形成均相乳液即制备得到多功能纳米探针。
所述的氟碳化合物为FC-77（全氟环醚），PFOB（全氟辛基溴），PFD（全氟萘烷）或PFMHP（全氟甲基环已基哌啶）中的至少一种。
所述的助表面活性剂为正丁醇、正己醇、正辛醇、丁二醇和丙三醇中的至少一种。
所述的增溶剂为：Tu-80（聚氧乙烯山梨醇酐单油酸酯），6501（椰油脂肪酸二乙醇酰胺），AEO-9（脂肪醇聚氧乙烯醚），Brij-35（月桂醇聚氧乙烯醚）或Triton X-100（聚乙二醇辛基苯基醚）中的至少一种。
所述的盐为氯化钠、氯化钾、氯化钙、氯化镁、磷酸二氢钠和磷酸氢二钠中的至少一种。
所述的光敏剂为吲哚菁绿、锌原卟啉中的至少一种。
主要通过将5-HT3抗体连接在壳聚糖载体上，加入氟碳化合物，形成氟碳示踪剂；将其与亲水性的光敏剂同时包裹于壳聚糖载体中，形成氟碳、光敏剂的纳米粒。该纳米粒中能实现超声成像功能、光敏剂具有光动力疗法作用。
本发明的优点在于：所制备的纳米粒中，5-HT3抗体具有靶向肠道的功能、氟碳具有超声成像功能、光敏剂具有光动力疗法作用。制备工艺简单，所得的产物稳定性好。
具体实施方式
以下结合具体实施例对本发明作进一步的详细描述。
实施例1
（1）壳聚糖的改性
在1份壳聚糖中，加入1份助溶的乙醇和10份二次水，同时加入1份NHS和EDC，再加入0.5份5-HT3抗体。室温下搅拌24小时后，将产物过滤，离心，洗涤，制成5-HT3抗体改性的壳聚糖。
（2）多功能纳米探针的制备
将35份改性的壳聚糖溶解于100份的水中，然后加入正丁醇25份、Tu-80 35份、氯化钠10份、吲哚菁绿10份，超声振荡至混合均匀、静置2小时，配制成乳液；加入10份氟碳示踪剂，在4℃及惰性气氛下搅拌30分钟，冷却至25℃，静置静置24小时，形成均相乳液即制备得到多功能靶向纳米探针。
实施例2
（1）壳聚糖的改性
在1份壳聚糖中，加入1份助溶的乙醇和10份二次水，同时加入1份NHS和EDC，再加入0.5份5-HT3抗体。室温下搅拌24小时后，将产物过滤，离心，洗涤，制成5-HT3抗体改性的壳聚糖。
（2）多功能纳米探针的制备
将40份改性的壳聚糖溶解于100份的水中，然后加入正丁醇25份、Tu-80 35份、氯化钾10份、锌原卟啉20份，超声振荡至混合均匀、静置2小时，配制成乳液；加入15份氟碳示踪剂，在4℃及惰性气氛下搅拌15分钟，冷却至25℃，静置静置24小时，形成均相乳液即制备得到多功能靶向纳米探针。
实施例3
（1）壳聚糖的改性
在1份壳聚糖中，加入1份助溶的乙醇和10份二次水，同时加入1份NHS和EDC，再加入0.5份5-HT3抗体。室温下搅拌24小时后，将产物过滤，离心，洗涤，制成5-HT3抗体改性的壳聚糖。
（2）多功能纳米探针的制备
将35份改性的壳聚糖溶解于100份的水中，然后加入丁二醇30份、Brij-35 40份、氯化钠15份、吲哚菁绿10份，超声振荡至混合均匀、静置2小时，配制成乳液；加入10份氟碳示踪剂，在4℃及惰性气氛下搅拌30分钟，冷却至25℃，静置静置24小时，形成均相乳液即制备得到多功能靶向纳米探针。
Claims (6)
1.一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于，通过将5-HT3抗体偶联在壳聚糖上，制备高分子载体化合物；将载体化合物和亲水性的光敏剂同时包裹氟碳化合物，形成氟碳、光敏剂的纳米粒，包括如下步骤：
（1）5-HT3抗体改性的壳聚糖
在1份壳聚糖中，加入1份助溶的乙醇和10份二次水，同时，加入1份N-羟基琥珀酰亚胺（NHS）和1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐（EDC），再加入0.5份5-HT3抗体，室温下搅拌24小时后，将产物过滤，离心，洗涤，制成5-HT3抗体改性的壳聚糖；
（2）多功能纳米探针的制备
将30-40份的5-HT3抗体改性的壳聚糖溶解于100份的水中，然后加入助表面活性剂20-30份、增溶剂30-40份、盐10-15份、光敏剂10-20份，超声振荡至混合均匀、静置2小时，配制成乳液；加入10-15份氟碳示踪剂，在4℃及惰性气氛下搅拌5-30分钟，冷却至25℃，静置静置24-48小时，形成均相乳液即制备得到多功能纳米探针。
2.根据权利要求1所述的一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于，所述的全氟化合物为FC-77（全氟环醚），PFOB（全氟辛基溴），PFD（全氟萘烷）或PFMHP（全氟甲基环已基哌啶）中的至少一种。
3.根据权利要求1所述的一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于所述的助表面活性剂为正丁醇、正己醇、正辛醇、丁二醇和丙三醇中的至少一种。
4.根据权利要求1所述的一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于所述的增溶剂为：Tu-80（聚氧乙烯山梨醇酐单油酸酯），6501（椰油脂肪酸二乙醇酰胺），AEO-9（脂肪醇聚氧乙烯醚），Brij-35（月桂醇聚氧乙烯醚）或Triton X-100（聚乙二醇辛基苯基醚）中的至少一种。
5.根据权利要求1所述的一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于所述的盐为氯化钠、氯化钾、氯化钙、氯化镁、磷酸二氢钠和磷酸氢二钠中的至少一种。
6.根据权利要求1所述的一种超声成像/光敏治疗的多功能靶向纳米探针的制备方法，其特征在于所述的光敏剂为吲哚菁绿、锌原卟啉中的至少一种。
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