Due to the quantum confined effect and unique optoelectronic properties, fluorescent semiconductor nanocrystals (quantum dots) play an important role in the tumor diagnosis. Our lab has long been engaged in the preparation of quantum dots (QDs) and their application as biomarkers in tumor diagnosis. Traditional quantum dots is mainly focused on Ⅱ-Ⅵ and Ⅲ-Ⅴmaterials which contain lead and cadmium. The cytotoxicity of heavy metal ions generated by the dissociation of quantum dots has greatly limited the further biological applications of these materials. In order to solve this problem, we have carried out the preparation of Cd-free CuInS₂ quantum dots and the growth kinetics research of the reaction system in recent years. Following on from our previous work, we developed a dual-modality molecular probe in tumor diagnosis based on CuInS₂@ZnS:Mn QDs.
    The synthesis of Mn-doped coreeshell structured CuInS₂@ZnS mainly comprised three steps, i.e., the preparation of fluorescent CuInS₂ seeds, the particle surface coating of ZnS, and the Mn doping of the ZnS shells. In combination with conventional fluorescence, fluorescence excitation, and time-resolved fluorescence measurements, the structure of CuInS2@ZnS:Mn QDs prepared under optimized conditions presented a Zn gradient CuInS₂ core and a ZnS outer shell, while Mn ions were mainly located in the ZnS shell, which well balanced the optical and magnetic properties of the resultant QDs. For the following in vivo imaging experiments, the hydrophobic CuInS₂@ZnS:Mn QDs were transferred into water upon ligand exchange reactions by replacing the 1-dodecanethiol ligand with dihydrolipoic acid-poly(ethylene glycol) (DHLA-PEG) ligand. The MTT assays based on HeLa cells were carried out to evaluate the cytotoxicity of the current Cd-free CuInS₂@ZnS:Mn QDs for comparing with that of water soluble CdTe QDs. Further in vivo fluorescence and MR imaging experiments suggested that the PEGylated CuInS₂@ZnS:Mn QDs could well target both subcutaneous and intraperitoneal tumors in vivo.
    The accepted article was benefited from the selfless help and inculcation of professor Mingyuan Gao in the whole experiment process and the writing of the article. Professor Gao devoted a lot of his time and energy on conceiving the research, providing guidance, discussing the data, revising and improving the manuscript. Thanks to his patient guidance, and my abilities on research and cooperation have been greatly improved. I am also grateful to Dr. Lihong Jing and other teachers and students in our lab.
                                                                                                                                                                                                           Ke Ding et al.