# 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 statistics presented by the World Health Organization, indicating a 1-in-8-10 risk of women developing breast cancer, are alarming. However, they also serve as a stimulus for intensive research in this field [42]. The list of selected and recently described targeted drug delivery systems based on Fe\({}_{3}\)O\({}_{4}\) NPs for potential application in breast cancer treatment is collected in Table 3. Much like the previously examined original studies, the primary active molecule in systems designed for potential breast cancer therapy is the anthracycline antibiotic--doxorubicin [44]. DOX has a broad spectrum of action but also has several undesirable effects: development of dose-dependent, cumulative, irreversible, and long-lasting cardiotoxic side effects [45]. An interesting proposal for a biocompatible nanocarrier dedicated to the delivery of DOX to breast cancer cell lines was presented by [PERSON] et al. (Figure 3) [46]. Fe\({}_{3}\)O\({}_{4}\) nanoparticles were initially coated with a silica layer using tetraethyl orthosilicate (TEOS) and modified with mesoporous silica SBA-15. Mesoporous silica with a high surface area should enhance loading efficiency and protect a drug. It is also capable of surface functionalization. In the next step, functional groups were introduced on the surface via trimethoxy vinyl silane (TMVS), which was used to modify the surface with the amino acid L-cysteine. At the same time, polyethyleneimine (PEI)--a branched polymer capable of DNA complexing--was modified by carboxymethyl-\(\beta\)-cyclodextrintrin (CM-\(\beta\)-CD) for the elimination of undesired reactions between PEI and serum components and for embedding folic acid (FA) into the CD cavity. FA should increase targeting to folate receptors that are overexpressed in many cancerous cells. Finally, PEI/CM-\(\beta\)-CD/FA was grafted onto mesoporous material. The pH-responsive core-shell nanocarrier demonstrated initial burst release due to the partial location of DOX molecules at the surface of the polymeric network. Faster DOX release was observed in an acidic environment due to repulsion between the drug molecules and the nanocarrier and partial destruction of hydrogel bonds that facilitated the drug release. The in vitro MCF-7 breast cancer cell viability assay showed that the half-maximum inhibitory concentration (IC\({}_{50}\)) was 0.511 ug/mL and 0.23 ug/mL for free DOX and DOX loaded in the nanocarrier. Hence, the utilization of the carrier results in lower cancer cell survival and a reduced dosage of DOX. The fluorescence microscopy imaging showed that the cellular uptake process was completed in 3 h. It also showed that only DOX-loaded nanocarrier induced chromatin fragmentation, while the nanosystem itself did not influence the morphology of breast cancer cells. Moreover, the fragmentation was more significant than for free DOX. Additionally, the nanocarrier was considered biocompatible because only a small, negligible hemolytic effect was observed for high dosage. The silica-coated magnetite nanoparticles (Fe\({}_{3}\)O\({}_{4}\)@SiO\({}_{2}\)) also served as the initial material for the nanocarrier, which was then modified with tragacanth gum derivative--a natural anionic polysaccharide characterized by a multibranched structure--and folic acid as a targeting agent [47]. Coating of magnetite nanoparticles with carboxymethyl tragacanth ensures a hydrophilic surface that protects against agglomeration, increases the dispersion of nanoparticles, and improves bioavailability. The protonation of carboxylic groups in polymeric shells in acidic environments leads to faster DOX release compared to physiological conditions. It is explained by repulsion interactions between protonated carboxylic groups and the drug molecules, and the breaking of some hydrogen bonds. Consequently, DOX diffusion into the acidic solution with conditions similar to tumor cells is much faster.