# Copper- and Iron-Based Nanoflowers in Cancer Theranostics
## 2 Synthesis Methods for Copper- and Iron-Based Nanoflowers
### Polyl Process  
After nearly thirty years of development, the polyol process has become a widely recognized and effective soft chemical method for synthesizing nanoparticles used in key technological areas. Polyols, along with traditional reducing agents, have proven to be highly efficient in producing metal nanoparticles, leading to the term \"polyol process\" [56]. First introduced in the late 1980s by [PERSON], [PERSON], and [PERSON], this colloidal chemistry method allows for the liquid-phase synthesis of finely divided metals from their oxides, hydroxides, or salts using polyols [57]. Magnetically induced hyperthermia has also advanced significantly, now reaching phase III clinical trials for cancer treatment.  
The polyol method is particularly favored for synthesizing flower-like magnetic nanoparticles (Figure 5), with substantial research focused on enhancing their magnetic heating capabilities. Improvements to the polyol process, such as controlling nanoparticle size and morphology through precise water addition or seeded growth methods, have been explored. It has been suggested that the polyol method offers more versatility than thermal decomposition, allowing better control over both particle size and the composition of the grains in the flower-like structures [82].  
[PERSON] et al., developed a fast and simple method for producing colloidably stable iron oxide nanostructures with excellent heating capabilities using the polyol process. This approach led to biocompatible single-core nanoparticles and nanoflowers. The study optimized nanoparticle heating rates by adjusting parameters like precursor concentration, polyol molecular weight, and reaction time. Polyacrylic acid facilitated the formation of efficient nanoheating agents--iron oxide nanoflowers (IONFs)--in just 30 min. The seeded growth method enhanced nanoflower size, improving heating efficiency with an intrinsic loss parameter of 8.49 nH m\({}^{2}\) kg Fe\({}^{-1}\). The colloidal stability of the nanoflowers was preserved through a ligand exchange protocol, where polyol ligands were replaced with sodium tripolyphosphate for long-term stabilization (Figure 6) [22].  
[PERSON] et al., synthesized iron oxide nanoflowers (IONFs) as innovative heating mediators for magnetic hyperthermia therapy (MHT) using the polyol method. The resulting NFs exhibited cluster-like geometry, providing excellent colloidal stability and high specific absorption rate (SAR) values. The study compared NFs of different sizes and coatings, focusing on stability, magnetothermal responsiveness, and in vitro behavior,  
Figure 5: Synthesis of stable iron oxide nanoflowers with simple and fast polyol synthesis. Reprinted (adapted) with permission from Ref. [22]. Copyright 2021 American Chemical Society.  
Figure 6: A schematic illustrating the simple one-pot thermal decomposition of Fe(acac)\({}_{3}\) in polyol synthesis is provided. In Step 1, single-core iron oxide nanoparticles (IONPs) are produced without poly(acrylic acid). In Step 2, iron oxide nanoflowers (IONFs) are formed with poly(acrylic acid). Finally, in Step 3, the stability of the resulting products in water is achieved by replacing the polyol ligand with sodium tripolyphosphate. Reprinted (adapted) with permission from [22]. Copyright 2021 American Chemical Society.  
including cytotoxicity and cellular localization, both with and without MHT. To facilitate simultaneous cellular imaging and therapy, the nanoflowers were coated or loaded with Rhodamine B (RhB), a red fluorescent dye with high quantum yield and photostability. The research also compared the in vitro behavior of RhB-loaded NFs and magnetoliposomes to assess their therapeutic and imaging potential under MHT [22; 83].