# 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
For this purpose, magnetite was initially covered with a silica layer and then combined with a metal-organic framework--mesoporous zeolitic imidazole framework -8 (ZIF-8)--to increase drug loading capacity. Subsequently, chitosan functionalized with a targeted ligand (folic acid) covered a magnetic core, and cisplatin (CPT) was loaded into the nanocomposite [86]. ZIF-8 is often studied as a versatile nanocarrier characterized by biocompatibility and biodegradability in acidic environments. Chitosan should increase magnetic core stability and bioavailability, while FA improves targeting efficiency. A murine tumor model proved the inhibition effect of CPT-loaded nanocarrier on cervical tumor growth, and the anticancer activity was higher than that for pure cisplatin. Moreover, the drug enclosed within the delivery system primarily accumulated at the tumor site due to enhanced tissue necrosis in the cervical tumor compared to pristine CPT. Folic acid was also attached as a targeting molecule to folate receptors to a magnetite core covered with hyperbranched glycerol (HPG) for curcumin delivery to cervical cancer [87]. Curcumin demonstrates the ability to damage HeLa cells, increasing reactive oxygen species generation and reducing the viability of cervical cancer cells. However, it requires protective carriers to increase its bioavailability and reduce high metabolism. HPG is a biocompatible polymer with a dendrimer-like structure that can be easily functionalized with targeting agents. The morphology of cells has not changed in the presence of the nanocarrier, but it has a negative impact on cell walls (normal and cancer cells) because cells aggregate due to electrostatic interactions. The CUR-loaded nanocarrier demonstrated considerable cell toxicity to tumor cells, which was time-dependent, and more toxicity was evaluated after 72 h than 24 h. The presence of FA increased selectivity towards cancer cells and cellular uptake. MRI studies showed the largest change in a reduction in signal enhancement in the HeLa cell line incubated with the CUR-loaded nanocarrier compared to other samples incubated with free CUR and the CUR-loaded nanocarrier without FA. It confirmed the observation from cellular uptake and cell viability studies. Another proposed solution involving FA concerns the delivery of doxorubicin using magnetite connected by a disulfide bridge to chitosan functionalized with folic acid [88]. A disulfide bond is relatively stable in low concentrations of glutathione (GSH), characteristic of extracellular fluids (2 uM). However, it is destroyed via redox reaction in higher GSH concentrations (2-10 mM in intracellular fluids). Importantly, GSH concentration in cancer cell cytoplasm is at least four times higher than in normal cells. In turn, chitosan with easily protonated amine functional groups upon acidic conditions acts as a pH-responsive polymer that entraps the active agent in its porous channel in physiological pH and releases the drug in an acidic tumor environment. Folate receptors mainly mediated the nanocarrier internalization. The DOX-loaded dual-responsive system inhibited tumors significantly, and the cellular uptake by HeLa cells was much higher than that of normal cells. Although pure DOX demonstrated better inhibition properties, it also caused a high bodyweight mass decrease in mice, suggesting systemic toxicity. In the case of bone cancer, the most common form in adults and children is osteosarcoma. The treatment of this cancer usually involves surgery and high doses of drugs, e.g., doxorubicin. Therefore, several nanocomposite systems were recently proposed for targeted delivery of active agents to the human osteosarcoma cell line (MG63). A magnetite-chitosan core-shell nanosystem was designed for DOX delivery to the MG63 cells by modifying chitosan with carboxylic acid functional groups participating in stable inclusion complex formation between Fe\({}_{3}\)O\({}_{4}\) and chitosan [89]. Additionally, folic acid was conjugated to the nanocarrier for targeting folate receptors.