蝎氯毒素靶向的白蛋白-金属卟啉纳米自组装体联合MRI 引导声动力治疗脑胶质瘤的实验研究

批准号:
81801724
项目类别:
青年科学基金项目
资助金额:
21.0 万元
负责人:
万倩
依托单位:
学科分类:
H2703.超声医学
结题年份:
2021
批准年份:
2018
项目状态:
已结题
项目参与者:
吴玫颖、邓志婷、乔阳紫、帖长军、王琳、程传力、万丽雯、邹莉娴
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中文摘要
声动力治疗为脑胶质瘤治疗提供了新契机。然而,声敏剂难以穿过血脑屏障、无法颅内示踪以及超声波介导的热效应易对正常脑组织产生损伤等问题限制了声动力治疗的应用。研究表明,蝎氯毒素能协助药物穿透血脑屏障并靶向脑胶质瘤;卟啉及其衍生物可与金属离子螯合形成金属卟啉用于声敏剂示踪。基于此,本项目拟将声敏剂二氢卟吩e6与锰离子螯合获得锰-卟啉,进而构建蝎氯毒素多肽靶向的白蛋白-金属卟啉纳米自组装体,实现声敏剂在脑胶质瘤中的靶向与渗透,借助磁共振成像观察其在肿瘤中的聚集,并引导超声定点激励声敏剂,以期达到精准声动力治疗脑胶质瘤的目的。项目前期研究制备了白蛋白-金属卟啉纳米自组装体,初步证实其在皮下胶质瘤模型具较好的声动力治疗效果。本项目将进一步研究蝎氯毒素多肽靶向的白蛋白-金属卟啉纳米自组装体在颅内原位脑胶质瘤的治疗效果。项目的成功实施有望建立一种安全有效的脑胶质瘤治疗方法,为声动力临床转化奠定科学基础。
英文摘要
Sonodynamic therapy (SDT) has recently emerged as a promising non-invasive therapeutic modality for malignant brain tumors. However, it is difficult for sonosensitizer to cross the blood-brain barrier, to be imaged in the deep brain and to be excited by ultrasound, which limits its application to glioma treatment. Evidences have demonstrated that chlorotoxin(CTX) peptides can help drugs to penetrate the blood-brain barrier and to deliver into the cancer cells. Also, many kinds of metalloporphyrins have been obtained through chelating some metal ions into porphyrins or their derivatives, giving them the ability to be imaged. In this project, we propose a novel approach to realize MRI-guided sonodynamic therapy of glioma through chlorotoxin-targeted albumin- -metalloporphyrin nanoassemblies. In brief, manganese ions will be chelated into chlorin e6, a new sonosensitizer, and further be encapsulated into CTX-targeted albumin nanoassemblies .With the help of CTX peptides, the resulting sonosensitizer would be delivered into the glioma and be imaged by magnetic resonance imaging. Based on the position information detected by MRI, ultrasound beam would be positioned on the sonosensitizer. The sonosensitizer will be excited by focused ultrasound, resulting in oxygen free radicals to kill the cancer cells. Our previous study have prepared albumin-metalloporphyrin nanoassemblies, which can inhibit the growth ofsubcutaneous xenotransplanted glioma. This project will further investigate the effectiveness, biosafety and mechanisms of imaging-guided sonodynamic therapy of intracranial glioma by chlorotoxin-targeted albumin- -metalloporphyrin nanoassemblies. Our study will provide a novel idea to realize the sonodynamic therapy of intracranial glioma and will expect to undergo clinical translation.
声动力治疗为脑胶质瘤治疗提供了新契机。然而,声敏剂难以穿过血脑屏障、无法颅内示踪;以及超声波介导的热效应易对正常脑组织产生损伤等问题限制了声动力治疗的应用。因此,本项目将声敏剂二氢卟吩e6与锰离子螯合获得锰-卟啉,进而构建白蛋白-金属卟啉纳米自组装体HSA-Ce6 NAs,实现了声敏剂在脑胶质瘤中的靶向与渗透,并借助磁共振成像观察所制备的白蛋白-金属卟啉纳米自组装体在肿瘤中的聚集。在磁共振引导超声聚焦系统引导下,证实所制备的白蛋白-金属卟啉纳米自组装体药物在皮下胶质瘤模型和颅内原位脑胶质瘤均具有较好的声动力治疗效果。项目的成功实施,建立了一种安全有效的脑胶质瘤治疗新方法,为声动力临床转化奠定科学基础。具体完成内容:.(1).成果制备了白蛋白-金属卟啉纳米自组装体HSA-Ce6 NAs;.(2).检测了HSA-Ce6 NAs的氧自由基产生能力及体外声动力治疗效果;.(3).验证了HSA-Ce6 NAs细胞内摄取与ROS提高水平;.(4).检测了HSA-Ce6 NAs的体内成像能力;.(5).MRI 引导下HSA-Ce6 NAs 联合超声有效抑制皮下移植瘤和原位胶质瘤的生长。.项目已发表SCI论文2篇,会议论文5篇,授权发明专利1项,培养研究生2人。.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Stepwise drug release from a nanoplatform under MR-assisted focused ultrasound stimulation
在 MR 辅助聚焦超声刺激下从纳米平台逐步释放药物
DOI:10.1016/j.cej.2020.128004
发表时间:2021-05-12
期刊:CHEMICAL ENGINEERING JOURNAL
影响因子:15.1
作者:Liu, Tianzhi;Wan, Qian;Chen, Hangrong
通讯作者:Chen, Hangrong
Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy
成像引导聚焦超声诱导纳米声敏剂的热和声动力效应协同增强胶质母细胞瘤治疗
DOI:10.1039/c9bm00292h
发表时间:2019-07-01
期刊:BIOMATERIALS SCIENCE
影响因子:6.6
作者:Wan, Qian;Zou, Chao;Zheng, Hairong
通讯作者:Zheng, Hairong
基于磁共振水特异性T1定量成像技术的非酒精性脂肪性肝炎早期检测研究
- 批准号:n/a
- 项目类别:省市级项目
- 资助金额:30.0万元
- 批准年份:2023
- 负责人:万倩
- 依托单位:
国内基金
海外基金
