# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 3.3. **Magnetite-Based Nanomaterials for Specific Cancer Treatment**
### Breast Cancer Treatment
The DOX-loaded nanosystem displayed high activity over MCF-7 breast cancer cells and cytoskeleton organization, while the pristine nanocarried had good biocompatibility. Another example of an absorbing carrier was designed using non-ionic polymers--polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP)--and two ligands to actively target breast cancer cells--\(\beta\)-estradiol for estrogen receptors and folic acid for folate receptors [52]. The selected ligands belong to the best-known breast cancer biomarkers. The polymers PVA and PVP were selected due to their widespread use in numerous pharmaceutical applications and non-ionic nature. The ligands showed a tumor-targeting effect and enhanced drug uptake but also stabilized nanoparticles. Alternative approaches suggested in recent scientific papers rely on drug delivery systems that are considerably simpler. An illustration is a nanocomposite composed of a magnetic core and CaCO\({}_{3}\), which exhibited promising properties in effectively inhibiting MCF-7 cell lines [53]. The oleic acid-modified magnetite core was coated with porous CaCO\({}_{3}\) using the coprecipitation method. The material demonstrated high loading efficiency (1900 \(\upmu\)g DOX/mg) and stability at physiological pH, while demonstrating efficient DOX release in acidic media. The experiments with human serum albumin solution indicated that the drug release was promoted by forming a protein corona--a protein coating on the surface of nanomaterials in biological fluids that improves biodistribution, biocompatibility, or cellular interactions. On the other hand, magnetite nanoparticles covered with citric acid (CA) were proposed as a potential DOX delivery system in the treatment of triple-negative breast cancer--an uncommon breast cancer subtype without an identified molecular target [54]. Citric acid is a popular surfactant, with one hydroxyl and three carboxyl functional groups, that stabilizes magnetite nanoparticles in aqueous suspensions. The in vitro studies were carried out using the 4T1 breast cancer cell line to study the metastatic nature of the cancer and the MDA-MB-468 breast cancer cell line characterized by lack of expression of estrogen, progesterone, and human epidermal growth factor receptors. In optimized formulations, the DOX-loaded nanosystem showed a synergistic effect on the cell cultures compared to pristine doxorubicin. The proposed mechanism is demonstrated in Figure 4. In brief, the nanoparticles are responsible for forming the reactive oxygen species that catalyze the Fenton reaction. At the same time, active oxygen species are formed during drug-induced apoptosis. The synergism results in better penetration and improved drug uptake. Additionally, active oxygen forms could be responsible for cell DNA damage. A distinctly different approach was suggested for a magnetic carrier prepared utilizing a natural porous silica structure, namely, diatoms [55]. Diatoms are algae characterized by biosilica with high mechanical stability and high surface area, biocompatibility, and  
Figure 4: Proposed anticancer mechanism of the DOX-loaded citric acid coated-magnetite nanoparticles. Reprinted from [54], _Pharmaceutics_ (2023). thermal and chemical resistance. Thus, the material is suitable for controlled drug delivery. A magnetic microrobot was fabricated using Thalassiosira weissflogii frustules as a biological template, followed by magnetite NPs adhering to the frustules' surfaces through electrostatic adsorption. In general, magnetic nano/microbots are fabricated using synthetic materials (expensive), living cells (difficulties in maintaining cell viability), and natural biological templates. The latter combines the beneficial features of high biocompatibility with the desired structural properties and can be combined with other components. The operation of micro/nanorobots is based on the ability to convert energy into motion, hence the growing interest in this group of systems, especially as the most sophisticated DDSs [56; 57; 58].