# 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 DOX-loaded material (high DOX concentration, 20 uM) was capable of osteosarcoma cell inhibition after 72 h (>60% cytotoxicity). The presence of FA resulted in a higher percentage of apoptotic cells in the DOX-loaded nanocarrier-treated MG 63 cells. According to a flow cytometric study, those cells could uptake more drug-loaded material than normal cells. After 4h of incubation, the cellular uptake was 85.46% for the material studied, while it was much lower for pristine DOX (38.19%) and slightly lower for the reference nanocarrier without folic acid (78.52%). Another strategy for improving DOX delivery to bone-related cancer was based on magnetite encapsulated in bioactive glass (BG), additionally functionalized with reactive amine groups [90]. BG particles are biodegradable and biocompatible because they are capable of bonding to the bone via forming a hydroxycarbonate apatite layer. Importantly, the biodegradation products (Ca, P, Si) demonstrate osteogenic potential. The nanocarFie\({}_{3}\)O\({}_{4}\)@BG is proposed as a potential filler in bone cavities affected by bone tumors. It had no significant effect on cellular growth in lower concentrations, while above 250 \(\mathrm{\SIUnitSymbolMicro g}\)/mL, a significant reduction in cell proliferation was observed. It was attributed to the degradation of BG inside cells, resulting in an influence on cell homeostasis (presence of BG ionic degradation products). DOX release from the Fe\({}_{3}\)O\({}_{4}\)@BG nanocarrier was pH-dependent. It was relatively slow in physiological conditions due to hydrogen bonds and electrostatic interaction between DOX and amine groups at the BG mesoporous surface. On the contrary, in an acidic environment, the protonated groups tended to be separated due to repulsive forces, resulting in faster drug release. On the other hand, a magnetic nanocarrier composed of Fe\({}_{5}\)O\({}_{4}\) and amine-functionalized \(\beta\)-cyclodextrinrin grafted graphene oxide was used for co-delivery of doxorubicin and melatonin (MLT) to increase apoptosis of osteosarcoma cells [91]. The composite nanocarrier was obtained in several synthetic steps. \(\beta\)-CD was functionalized with pH-responsive dendrimer with amine functional groups. Then, it was grafted with graphene oxide to obtain a platform with different functional groups. In the final step, magnetic NPs were synthesized on this platform. The cell viability did not fall below 85% at all treated doses of the nanocarrier (10-1280 \(\mathrm{\SIUnitSymbolMicro g}\)/mL). The co-delivery of DOX and MLT resulted in a synergistic antitumor effect because iMLT effectively protected normal cells against DOX cytotoxicity while enhancing antibiotic toxicity to cancer cells. The properties of \(\beta\)-CD were also applied for paclitaxel encapsulation in Fe\({}_{3}\)O\({}_{4}\)@ \(\beta\)-CD nanopowders and thin films deposited by the matrix-assisted pulsed laser evaporation (MAPLE) technique [92]. The PTX-loaded films decreased the MG 63 cell viability by 85%. There is considerably less focus on targeted magnetite-based systems for drug delivery in treating cancers other than those mentioned above, but there are several noteworthy solutions have been proposed. Albumin-perfluorohexane (PFH)-magnetite nanoparticles were produced for cisplatin delivery to gastric cancer cells [93]. PFH is widely used as an oxygen carrier to overcome hypoxic conditions and thus increase drug delivery to CPT-resistant cancer cells. The gastric cell growth inhibition strongly depended on the CPT dose on the magnetic nanocarrier, but the presence of protein coating increased the inhibition effect compared to free CPT. The enhanced induction of apoptosis resulted from the improved formation of intracellular reactive oxygen species. In turn, the system already mentioned several times, containing a cover composed of chitosan and polyethylene glycol, with conjugated folic acid, was also used to deliver PTX for fibrosarcoma--a rare cancer type affecting fibroblasts [94].