# Copper- and Iron-Based Nanoflowers in Cancer Theranostics
## 4 Synthesis Methods and Applications of Flower-like Copper- and Iron-Based Nanostructures
### Copper-Based NFs
\begin{table}
\begin{tabular}{c c c c} \hline \hline
**Nanoflower Type** & **Reaction Parameters** & **Main Findings** & **Ref.** \\ \hline \multirow{8}{*}{CuS-MnS\({}_{2}\)} & Temperature: 100 \({}^{\circ}\)C & \multirow{8}{*}{Pretential use as the transonic agents for MRI and PDT/PTT for cancer.} \\  & Reaction time: 4 h & \\ \cline{1-1}  & Precursors: Thioacetamide, CuCl\({}_{2}\)\({}_{2}\)H\({}_{2}\)O, & \\ \cline{1-1}  & MnCl\({}_{2}\) 4H\({}_{2}\)O, (15:5:1 mol/mol/mol); & \\ \cline{1-1}  & Surfactant sodium & \\ \cline{1-1}  & dodecylbenzesulphonate; & \\ \cline{1-1}  & Solvent: H\({}_{2}\)O; & \\ \cline{1-1}  & Washing solvents: EtOH, H\({}_{2}\)O. & \\ \cline{1-1}  & Temperature: 150 \({}^{\circ}\)C & \\ \cline{1-1}  & Reaction time: 6 h & \\ \cline{1-1}  & Precursors: Cu(NO\({}_{3}\))\({}_{2}\); & \\ \cline{1-1} NGO–FA–CuS & Reducing agent: thioglycolic acid; & \\ \cline{1-1}  & Solvent: Type 1 H\({}_{2}\)O; & \\ \cline{1-1}  & Washing solvents: EtOH, DI H\({}_{2}\)O; & \\ \cline{1-1}  & Other materials: Folic acid-conjugated & \\ \cline{1-1}  & nanographene oxide. & \\ \cline{1-1}  & Temperature: room temperature; & \\ \cline{1-1}  & Reaction time: 4.5 h; & \\ \cline{1-1}  & Precursor: CuCl\({}_{2}\); & \\ \cline{1-1} Cu-EGCG-ICG-DOX & Solvent: triethanolamine. & \\ \cline{1-1}  & Drugs: (\(-\))))))))))))))))))} \\ \\ \\ \\ \\ \\ \\ \\ \end{tabular}
\end{table} 
Table 6. Synthesized copper-based nanoflowers under diverse reaction conditions and their main findings. [PERSON] et al., synthesized self-assembled Cu HNF loaded with epigallocatechin-3-gallate (EGCG), indocyanine green (ICG) and doxorubicin hydrochloride (DOX) (referred to as ICG \(\supset\) EDOX), based on the metal coordination effect, hydrophobic interactions and \(\pi\)-\(\pi\) stacking between the reagents. EGCG was used for its biocompatibility, ICG works as an excellent photoabsorbing agent causing green fluorescence, and DOX is a common drug used against cancer. After the characterization of the nanomaterial, it was found that DOX made up 42.1 wt%, indicating high drug load efficiency. The produced HNF exhibited responsive behavior to acidic pH (a characteristic of TME), releasing ICG \(\supset\) DOX at a rate of 13.5% at a pH = 7.4 and 33.1% at a pH = 5 (both measurements were conducted 108 h post injection). The synergetic effect between the HNF and PTT became obvious when NIR laser irradiation was applied at a pH = 5, and the release percentage of ICG \(\supset\) DOX increased up to 60.8%. The in vitro cytotoxicity of HNF was tested on murine mammary carcinoma (4T1) cells. The most efficient method proved to be ICG \(\supset\) DOX combined with laser irradiation, as the viability of 4T1 cells was valued at 47.9%. Moreover, no hemolysis of red blood cells was observed after they were being treated with ICG \(\supset\) EDOX. Concerning in vivo experiments, it was noted that mice with administrated ICG \(\supset\) EDOX did not exhibit hair loss, weight loss and tissues damages so severely compared to mice who were only administrated DOX. [PERSON] et al., synthesized PEG Cu\({}_{7}\)2S4/5 MoS2 composite NFs (CSMS-PEG CNFs) in a one-pot approach, using the solvothermal method. The in vitro cytotoxicity of CSMS-PEG CNFs was examined on 4T1 cells. The sole use of NFs did not influence the cells' viability, whereas the highest concentration of NFs (200 ug mL\({}^{-1}\)), combined with laser irradiation, imposed death on 78% of tumor cells. The photothermal conversion of CSMS-PEG CNFs was tested in different concentrations. It was proved that under a laser irradiation of 808 nm, the sample with 200 ug mL\({}^{-1}\) showed the highest PT properties to be 20.9 \({}^{\circ}\)C in 500 s, therefore proving a dose-dependent correlation. Moreover, in vivo experiments on mice showed that CSMS-PEG CNFs combined with laser irradiation have a great therapeutic effect on 4T1 cells without a reoccurrence of the tumor [120]. [PERSON] et al., synthesized CuS NFs and tested them as a multimodal nanomaterial.