胰腺癌LyP-1靶向性磁共振—荧光双模态分子探针实验

摘要

Objective To construct the LyP-1 targeted MR fluorescence dual-modality molecular probe for pancreatic cancer,and to observe its features and MRI charicteristics.Methods The 50 nm MR-fluorescent dual-modality molecular probe with surface modified with cyclic nine-amino acid peptide LyP-1 (Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly Cys) was rationally designed.Whether the molecular probe could specifically recognize the pancreatic cancer cells were validated by the combination of fluorescent imaging and MR T2WI.Results The new MR-fluorescent dual-modality molecular probe anchored with LyP-1 could be used for the fluorescent imaging and MR T2WI of pancreatic cancer in mouse.And the molecular probe was demonstrated to be effective in conjugating with pancreatic cancer cells on fluorescent images and caused obvious MR signal reduction under T2 relaxometry in vitro.In vivo experiment,the molecular probe could be used for fluorescent labeling tumor tissue and detecting orthotopic pancreatic cancer in C57BL/6 mouse as MR contrast agent.Conclusion The LyP1 immobilized MR-fluorescent dual-modality molecular probe can actively target to mouse orthotopic xenograft of pancreatic cancer,which is hopeful to the application in early probing and diagnosis of pancreatic cancer by multimodal imaging.%目的 构建胰腺癌LyP-1靶向性磁共振—荧光双模态分子探针,观察其表征并进行MR显像.方法 构建50 nm核壳结构的磁共振—荧光双模态介孔探针,表面经环形多肽LyP-1(Cys-Gly-Asn-Lys-Arg-Thr-Arg-Gly-Cys)修饰,通过荧光及MR T2WI联合成像,验证该分子探针能否特异性识别并结合胰腺癌细胞.结果 新型LyP-1靶向性磁共振—荧光双模态分子探针可用于小鼠原位胰腺癌的荧光显像和磁共振成像,可有效结合胰腺癌细胞并在体外使T2WI信号明显降低.体内实验表明,该分子探针可与荧光标记的胰腺癌组织靶向结合,并作为MRI对比剂显示C57BL/6小鼠原位胰腺癌.结论 LyP-1靶向性磁共振—荧光双模态分子探针可靶向性地高效结合原位移植的小鼠胰腺癌细胞,用于早期胰腺癌诊断的转化研究.