中文摘要：

设计、合成了一类新型谷胱甘肽（glutathione,GSH）和凋亡酶-3（Caspase-3）响应的环肽分子荧光探针.该类探针主要由能量共振转移（FRET）分子荧光对、Caspase-3特异性识别多肽序列和GSH响应双硫键组成,分为不含穿膜肽序列（CP）和包含穿膜肽序列（cp CP）的两种不同环肽分子荧光探针.2种环肽分子荧光探针均能实现在GSH和Caspase-3同时存在情况下的精确成像,同时具有良好的响应性、特异性和高信噪比.该类环肽分子荧光探针在细胞培养环境中具有良好的稳定性和生物相容性.利用该探针,可以实现对星形孢菌素（STS）诱发的细胞凋亡进行实时、原位的成像监测,并对抗肿瘤药物阿霉素（DOX）和顺铂（cisplatin）诱导的细胞凋亡进行成像.这种具有多重响应并能用于精确成像的分子荧光探针将极大地促进疾病的精确诊断.

英文摘要：

Here, we reported two cyclic peptide fluorescent probes for simultaneous glutathione（GSH） and Caspase-3 imaging. The cyclic peptide fluorescent probes were composed of 5（6）-carboxylfluorescein（FAM）/4-（dimethylaminoazo）benzene-4-carboxylic acid（dabcyl） fluorescence resonance energy transfer（FRET） pair, Caspase-3 specific peptide sequence Asp-Glu-Val-Asp（DEVD）, glutathione（GSH） responsive disulfide bond, with Arg-Arg-Arg-Arg（RRRR） cell penetration peptide unit（short as cp CP） or without cell penetration peptide（short as CP）. Due to the FRET effect between FAM and Dabcyl in CP and cp CP, the FAM fluorescence was quenched with high efficiency. GSH could cleave the disulfide bond in the probes, but it would not terminate the intracellular FRET effect. And then, Caspase-3 would further recognise and cleave the DEVD peptide sequence, which would terminate the FRET process and subsequently induce dramatically fluorescence enhancement. The fluorescence recovery of the cyclic fluorescent probe was studied with or without the presence of GSH and/or Caspase-3. The fluorescent probe exhibited good stability in cell culture medium including DMEM, MEM, RMPI1640 and trypsin. And also, the cell cytotoxicity of CP and cp CP was measured against Hela cells using MTT assay. Benefitting from the RRRR cell penetration peptide sequence, cp CP could efficiently penetrate into cells. Using staurosporine（STS） as the cell apoptosis inducer, the Caspase-3 related cell apoptosis could be observed and the real time cell apoptosis was monitored in situ using the fluorescence recovery of cp CP. And also, doxorubicin（DOX） and cisplatin induced cell apoptosis could be monitored using cp CP as the reporter, which indicated that cp CP could be used as a tool for therapeutic efficacy evaluation. This dual-locked fluorescent probe design could extensively improve the precision for disease diagnose. Moreover, this type of cyclic peptide fluorescent probe is a versatile platform for multi-analyte imag