# Recent Progress and Challenges Regarding Magnetic-Based Nanoparticles for Targeted Drug Delivery
## 3.3. **Magnetite-Based Nanomaterials for Specific Cancer Treatment**
### Treatment of Other Cancers
The human hepatocellular carcinoma (HepG2) cells incubated with the DOX-loaded carrier demonstrated higher doxorubicin uptake than those incubated with pure DOX using analogous concentration. It was also suggested that the endocytosis pathways in endothelial and epithelial cells affect the interactions between the DOX-loaded nanocarrier and cells upon alternating magnetic field. In turn, the combination of magnetite and boron nitride was used to potentially increase the synergistic chemodynamic, photodynamic, and immune therapy [72]. Boron nitride nanosheet (\"white graphene\") demonstrates low toxicity, capability of chemical bond formation, biocompatibility, and biodegradability. Additionally, PEG, synthesized via benzoic mine, was introduced onto the nanocomposite surface to stabilize DOX release towards cancer cells and pH-responsiveness. The in vivo tests showed that the application of the DOX-loaded nanocarrier resulted in more significant tumor inhibition than pure DOX. The liver cellular uptake studies showed the influence of the DOX-loaded nanocarrier on cell morphology. It was suggested that improved cellular drug uptake resulted from the DOX-loaded carrier bypassing the P-glycoprotein efflux system in cancer cells, which helped to eliminate drug resistance. Thus, the mandatory factor affecting nanocarrier-cell interactions is again endocytosis pathways in endothelial/epithelial cells. The histopathological studies indicated nuclear shrinkage and cytoplasmic leakage of liver tumors, while no pathological changes were observed in other organs. In the original paper of [PERSON] et al. [73], another organic unit was used to modify the magnetite surface--deoxycholic acid derivative combined with folic acid. Cholic acid and its derivatives should improve the stability of drug metabolism and confer selectivity towards the liver. Therefore, magnetite initially functionalized with amine functional groups participated in a reaction with formyl deoxycholic acid (FDCA) and folic acid (FA) to obtain an FDCA-FA-Fe\({}_{3}\)O\({}_{4}\) nanocarrier of doxorubicin. The material studied demonstrated excellent blood compatibility in a specific concentration range, thus ensuring safe DOX delivery in the blood. Importantly, cellular uptake studies showed selectivity of the nanocarrier towards hepatoma cells due to the presence of FDCA, while FA was responsible for cancer cell targeting. Moreover, apoptosis staining proved a low concentration of DOX-loaded nanocarrier in viable cells while being strong in apoptotic cells. It is also significant that the drug carrier selectively targeted hepatocellular carcinoma cells (HepG2) compared to esophageal carcinoma cells (K150). Additionally, Western blotting was applied to analyze the expression of caspase-3 protein, necessary in the early stage of apoptosis, in HepG2 cells. The experiments confirmed the influence of DOX-loaded nanocarrier on increasing caspase-3 expression. Another solution for targeted DOX delivery to the HepG2 cells was based on a system composed of magnetite nanoparticles and Zn-Al layered double hydroxides (Zn-Al LDHs) [74]. Zn-Al LDH nanosheets should protect magnetite against aggregation and assure uniform decoration, while Fe\({}_{3}\)O\({}_{4}\) nanoparticles should stabilize the composite structure and prevent restacking of the nanosheets. The nanocarrier demonstrated high loading efficiency (0.23 g/g) and a pH-responsive release profile. The DOX-loaded Fe\({}_{3}\)O\({}_{4}\)/Zn-Al LDH nanocarrier showed a significant inhibition effect on the proliferation of HepG2 liver cancer cells. The drug-free nanocarrier had no significant influence on cell morphology, confirming good biocompatibility, while the presence of the DOX-loaded carrier resulted in an apoptotic effect that increased with increasing drug concentration. Literature reports also encompass alternative active compounds within delivery systems targeting liver cancer cells. Sorafenib (SFB) inhibits the formation of nucleic acids by connecting to DNA.