**4. Chalcogenide QDs: synthesis methods, modification, cytotoxicity, and application in cancer cell imaging**

 Beside to graphene and graphene oxide [ 51 ], transition metal dichalcogens (TMDs), which belong to a large family of layered compounds, have attracted a lot

#### **Figure 8.**

 *The typical approaches for the synthesis of MoS2 QDs.* 

of attention in the field of drug delivery and imaging [ 52 , 53 ]. Among TMDs, molybdenum disulfide (MoS2) is used more than in the fields of drug delivery, sensing and imaging [ 54 , 55 ]. MoS2 QDs due to features such as water-solubility, biocompatibility, high stability, less toxicity, and high surface-area has attracted enormous interest [ 56 , 57 ]. There are many methods for the preparation of MoS2 QDs, including chemical intercalation, electrochemical exfoliation, liquid solvent exfoliation, electron Fenton reaction, and hydrothermal reaction which are shown in **Figure 8** .

 Several studies have investigated the use of MoS2 QDs in cancer cell imaging. Roy et al. used free folic acid-sensitive MoS2 QDs based "turn-off" nanoprobes for bioimaging of cancer cells. Their results showed that the FA-pretreated B16F10 cancer cells show higher population of dimmed fluorescence compared to untreated cancer cells and HEK-293 normal cells ( **Figure 9A** ) [ 58 ]. In another study, Liu and colleagues produced MoS2 QDs through a facile one-step and low cost and green method for bioimaging applications. They reported that blue luminescence was observed inside the HeLa cells, indicating that the QDs had penetrated the cell and mainly localized in the cytoplasm region ( **Figure 9B** ). In addition, they stated that molybdenum disulfide quantum dots were not toxic on cells and the morphology of cells remained normal [ 59 ]. Shi and co-worker introduced a Bottom-up hydrothermal approach for the preparation of MoS2 QDs with Na2MoO4 2H2O as molybdenum source and GSH as sulfur source. The in vitro result showed that blue fluorescence was observed in the cytoplasm of SW480 cells, which indicating that GSH-MoS2 QDs has successfully entered the cell. In the in vivo study, the GSH-MoS2 QDs were injected into the mice with

#### **Figure 9.**

 *Application of MoS2 QDs in cancer cell imaging. (A) Confocal microscopic images of HEK-293 and B16F10 cells after treating MoS2 QDs in FA-pretreated and untreated cells. Reprinted with permission from [ 51 ]. (B) Confocal fluorescence microphotograph of HeLa cells incubated with MoS2 QDs. Reprinted with permission from [ 52 ]. (C) In vitro fluorescence imaging of SW480 tumor cells with MoS2QDs; in vivo fluorescence images of mice bearing renal carcinoma tumors pre- and post-injection (1 h and 24 h) of MoS2QDs. The red circle in pictures indicated tumor region. Reprinted with permission from [ 53 ].* 

colon cancer via the tail vein. After the injection of QDs, the contrast of the tumor area increased and the environment around the tumor became blue ( **Figure 9C** ). In addition, the results of the biocompatibility test as well as histological analysis showed that GSH-MoS2 QDs do not have obvious toxicity on SW480 cells and no abnormality was observed in different tissues such as heart, kidney, and lung [ 60 ].
