Ze-hui LIU,Jin HUANG,Ming-hua ZENG,Zheng YIN

(1.Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China；2.Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources,Guangxi Normal University,Guilin 541004，China）

T3-12

Assembly of a highly stable luminescent Zn5 cluster and application to bio-imaging

Ze-hui LIU1,Jin HUANG1,Ming-hua ZENG2,Zheng YIN2

(1.Shanghai Key Laboratory of New Drug Design,School of Pharmacy,East China University of Science and Technology,Shanghai 200237,China；2.Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources,Guangxi Normal University,Guilin 541004，China）

OBJECTIVETo explore a novel pH-sensitive fluorescent probe for in vivo tumor imaging.METHODSZn5 were obtained in 140℃ after mixed with MeOH,water,Zn(NO3)2·6H2O,H4L and trimethylamine.The fluorescence spectra of Zn5 with the same concentration in different pH aqueous solutions were detected.And the stability of Zn5 was investigated by time dependent fluorescence emission spectra of Zn5 in BSA aqueous solution and 5.0%serum solution.Then,the cytotoxicity of Zn5 was detected by MTT assays.To clarify whether a similar fluorescence response occurs in biological organisms,HeLa cells were pretreated with probe Zn5(0.5 μmol·L-1)and fluorescence imaging were collected for targeting lysosomes in living cells because of lysosomes′acidic microenvironment.The A375 tumor-bearing mice were used to assess the imaging ability of Zn5 in vivo.Mouse tumor xenografts were established by injection of A375 cells with 2×106cells per f l ank.Probe(1 μg·g-1)was administered to mice by injection.Images were obtained using IVIS Spectrum CT Imaging System.RESULTSThere is a 11-fold intensity increasing as the pH values changing from 8 to 2.The almost unchanged emission intensities suggest Zn5 is stable in both BSA and serum.Zn5 has negligible cytotoxicity for HeLa,293T and CHO-K1 cells.Zn5 can selectively display lysosomes in living cells.Both the 2D and 3D images in vivo distinguish the tumor from other tissues with good fluorescence contrast.CONCLUSIONThe high chemical stability,emission in the Vis/NIR range,pH sensitivity,a pKa located in the tumor pH range,and low toxicity make Zn5 is suitable for application as a pH-sensitive fluorescent probe for bio-imaging.

3d-metal coordination cluster; bio-imaging fluorescence probes; pH sensitivity;Zn clusters

The project supported by Distinguished Young Scholars(21525101);and the NSFC(91422302,and 21371037)

Jin HUANG,E-mail:huangjin@ecust.edu.cn;Ming-hua.ZENG,E-mail:zmh@mailbox.gxnu.edu.cn